In October 2019, a 66-year-old male presented with discomfort on the right side of his waist and was admitted to Jiaozhou Renmin Hospital, China. Initial ultrasound revealed hepatic space-occupying lesions. Subsequent contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI) of the abdomen conducted on 2019-10-22 confirmed multiple lesions in the inferior segment of the right liver lobe. Additionally, the CECT identified cirrhosis of the liver. Laboratory investigations revealed a positive hepatitis B virus (HBV) status with a viral load of 5.10 x 10^3 IU/mL and an alpha-fetoprotein (AFP) level of 41.56 ng/mL. No intervention was initiated. On 2019-10-23, the patient was transferred to our hospital for detailed assessment and subsequent treatment. His medical history of hypertension or diabetes was unremarkable. Physical examination on arrival revealed a flat abdomen with mild right upper quadrant tenderness, although there was no evidence of weight loss or lymphadenopathy. The patient’s Eastern Cooperative Oncology Group (ECOG) score was rated as 1. His liver function was categorised as Child–Pugh class A, with a blood alpha-fetoprotein (AFP) level of 41.28 ng/ml. A positron emission tomography-computed tomography (PET-CT) scan () on 2019-10-28 demonstrated an enlarged right hepatic lobe measuring 95 mm×56 mm. Multiple lymph node metastases around the pancreatic head region, posterior to the bilateral diaphragmatic crus and at T10 and T12 on the right side of the vertebral bodies were identified. Additionally, extrahepatic metastatic involvement was noted in the right erector spinae muscle and the T12 vertebral body. The diagnosis was established as Barcelona Clinic Liver Cancer (BCLC) stage C HCC (equivalent to China Liver Cancer [CNLC] stage IIIb) as shown in. Given his unresectable tumour, coupled with a Child–Pugh classification of A, a diagnosis of BCLC stage C and an ECOG-PS score of 1, a first-line treatment regimen was initiated for the patient, involving a combination of immunotherapy and targeted therapy. On 2019-10-30, the patient received 200 mg of sintilimab intravenously (on day one every three weeks) plus 200–400 mg BID of sorafenib orally, along with antiviral therapy (tenofovir disoproxil fumarate: 300 mg orally once a day). After six treatment cycles, an evaluation conducted on 2020-05-21, revealed a significant therapeutic response. His disease achieved PR with a remarkable 60% reduction in the size of the target lesions, measured at 38 mm×23 mm according to RECIST criteria. Moreover, all extrahepatic metastases had been resolved, with the exception of a solitary lymph node metastasis adjacent to the T12 vertebra, measuring ~ 0.8 cm along its short axis with increased glucose metabolism (). The patient’s AFP levels had decreased substantially from 41.28 ng/ml to within the normal range (as shown in ), while his liver function remained unimpaired. Furthermore, antiviral therapy had effectively reduced HBV-DNA levels to less than 1.0 x 102 IU/mL, and no adverse events (AEs) were reported during the course of the systemic treatment. The patient continued the therapy for approximately one and a half years. A CT scan conducted on 2021-03-29, revealed a further reduction in the dimensions of liver lesions, now measuring 17 mm×28 mm. This significant response, amounting to a 70% reduction (deep response), along with the resolution of extrahepatic metastasis, prompted the consideration of surgical intervention. On 2021-04-26, a laparoscopic hepatectomy targeting segment 6 (S6) was performed under general anaesthesia. Post-operative pathological assessment confirmed HCC, with post-treatment response evident in the large necrotic area and negative resection margin. A small region of moderately differentiated HCC was encapsulated by fibrous tissue hyperplasia with hyaline degeneration and scattered inflammatory cell infiltration ). During the post-operative period, no adverse events or complications were observed, and the patient’s liver function remained within normal limits. The patient had an uneventful recovery, without the need for additional clinical intervention. A subsequent follow-up, including a PET-CT examination on 2021-04-26, revealed no clinical evidence of disease (). Concurrently, analysis via CTCBIOPSY® unveiled a circulating tumour cell count of two per 5 mL of blood, which is considered to be at a level indicating less possibility of disease recurrence (). From April 2021 to October 2021, the patient sustained a combined regimen of sorafenib and sintilimab for approximately six months. At the follow-up on October 31, 2023, the patient showed no signs of disease recurrence and remained on anti-HBV therapy.