A 71-year-old man, a former office clerk, was admitted to the First Affiliated Hospital of Chongqing Medical University on December 4, 2020 with a chief complaint of a 22 mm × 31 mm lesion observed on chest computed tomography (CT) since November 26, 2020. As seen in Fig. a and b, the lesion was located in the lower lobe of the left lung with irregularly lobulated shape, spiculations, and pleural invasion. This patient had no symptoms in daily life. He had smoked 10 cigarettes a day for 30 years in the past and had quitted smoking for 6 years. He had neither chronic disease nor a family history of cancer. After admission to the Thoracic Surgery unit, he completed the preoperative workup that showed: carbohydrate antigen 19-9 (CA19-9) at 62.2 U/ml (normal range, 0–27.0 U/ml) and carcinoembryonic antigen (CEA) at 225.1 mg/ml (normal range, 0.2–10.0 mg/ml). No metastasis was found on head CT and whole body bone scan. Contraindications to surgery were excluded by pulmonary function test, electrocardiogram, and echocardiogram. Radical resection of the pulmonary carcinoma and thorax adhesiotomy on thoracoscopy under general anesthesia was performed successfully on December 9, 2020. Intraoperative frozen pathology revealed a cancer. The postoperative pathological examination results revealed an invasive adenocarcinoma of the left lower lung. The proportions of tumor growth patterns of the papillary, acinar, micropapillary, and solid parts were 55%, 30%, 10%, and 5% respectively. No cancer involvement was found in the incisal margin of the bronchus and lung. Metastasis was found in No.5, No.7, No.10, No.11 and No.12 groups of lymph node. No.6, No.8, and No.9 groups of lymph node were not involved. The final diagnosis was invasive adenocarcinoma of the left lower lung classified stage IIIA (T2aN2M0). The result of lung cancer gene detection using paraffin section showed L858R mutation in exon 21 of the EGFR gene along with G12A/V/R/C and G13C mutations in exon 2 of the KRAS gene. Chemotherapy was not given because of the patient's weakness and unwillingness. Before EGFR-TKI selected, we noticed some reticular opacities and a few ground-glass opacities in the right lower lung that affected more than 5% of any lung zone. Therefore, the patient was considered to have ILA. Considering the low risk of ILD, almonertinib (110 mg per day) was chosen as first-line treatment and started on January 24, 2021. This patient complained of dyspnea in April 2021 and his activity tolerance decreased significantly. He could only tolerate walking slowly on a flat road. Chest CT (April 23, 2021, Fig. ) performed at the outpatient showed postoperative changes in the left lung and ILD in the lower lobe of the right lung. No obvious abnormalities were found on whole-body bone imaging. After stopping almonertinib on May 3, 2021, he still had dyspnea. Thus, he was admitted to the first branch of our hospital. As seen in Fig., a repeat chest CT on May 25, 2021 showed an increase in the lesions of ILD in both lungs. The results of his antinuclear antibody, antineutrophil cytoplasmic antibody, myositis antibody, anticyclic citrulline polypeptide antibody, rheumatoid factor, and creatine kinase were negative. Pulmonary function examination showed restrictive ventilation dysfunction and normal diffusion function. His dyspnea did not improve after symptomatic treatment with phlegm removal and anti-asthmatic. For further treatment, the patient was admitted to our hospital on June 3, 2021. Routine tests were requested. Blood gas analysis carried out under a nasal catheter oxygen inhalation of 2 L per minute showed 7.44 for pH, 42 mmHg of arterial partial pressure CO2, 85 mmHg of arterial partial pressure of O2, and 97% of oxygen saturation. His oxygenation index was 293 mmHg. Hemoglobin was 125 g/L. Infection-related indicators such as white blood cell count, percentage of neutrophils, procalcitonin level, and C-reactive protein were normal. Routine blood tests also revealed normal absolute value and proportion of eosinophils and lymphocytes. There were no abnormalities in liver and kidney function tests, electrolytes, and coagulation function. Cellular immune function monitoring showed CD4 + and CD8 + T cells were 392 per microliter and 143 per microliter respectively. The ratio of CD4 + and CD8 + T cells was 2.74. The specific serum IgM antibodies against influenza A and B virus, respiratory syncytial virus, adenovirus, chlamydia pneumoniae and mycoplasma pneumoniae were negative. The serum (1, 3)-β-D-glucan test and galactomannan detection were negative. Bronchoscopy and bronchoalveolar lavage were not performed due to his respiratory failure and weakness. We organized multidisciplinary discussions. He has never been exposed to dust. He had no history of hair dyeing, keeping pets, or sensitizing substance exposure. He never raised or contacted pigeons. During almonertinib administration, he mainly stayed at home. He did not go to the jungle, park, or other special environments. He did not change his living and eating habits. Amiodarone, immune checkpoint inhibitors, or other drugs that can induce ILD were not used previously. He did not receive radiotherapy or chemotherapy after the operation. The absolute value and proportion of eosinophils in the routine blood were not high. Infection-related indexes were not high. There was no abnormality in connective tissue disease (CTD)-related immune indexes screening. There was no manifestation of heart failure. According to imaging characteristics and negative whole body bone imaging, there was insufficient evidence of tumor recurrence. Based on the above analysis, we excluded eosinophilic pneumonia, hypersensitivity pneumonitis, pulmonary infection, CTD-ILD, heart failure, tumor recurrence, and other drugs-induced lung disorders. Considering the onset of ILD 3 months after taking almonertinib, almonertinib-induced ILD was evoked. Acetylcysteine 0.6 g q8h was used for antioxidation. Bailing capsule 1 g q8h was given as adjuvant treatment for ILD. On June 4, 2021, methylprednisolone 40 mg q12h was administered intravenously, supplemented by calcium tablet and stomach protection drugs. The patient's respiratory condition gradually improved on this treatment. On June 8, 2021, high resolution lung CT showed an improvement in the interstitial inflammation of the lower lobe of the right lung. On June 10, 2021, methylprednisolone dosage was reduced to 40 mg per day. On June 15, 2021, routine blood, liver, and kidney function tests and electrolyte were tested and showed no obvious abnormality. The patient was given oral prednisone tablets 40 mg per day and he was followed up regularly in the outpatient department. Prednisone dosage was gradually reduced. On July 9, 2021, repeat chest CT showed a significant reduction in the interstitial inflammation. So far, the patient's respiratory condition is stable. The patient tolerated this therapeutic schedule well with no other side effect.