A 5-month-old girl was admitted to our department due to a complaint of "stool color has been light for more than 20 days". During the 1.5 months prior to this hospitalization, the child sought medical attention at a local hospital due to poor weight gain. Abdominal ultrasound revealed gallbladder stones. She had no history of blood transfusion, no apparent history of medication, infection, or other relevant medical conditions. As the child had no apparent symptoms at that time, no specific treatment was initiated. About three weeks later, the child's parents noticed that the color of the stool had become lighter and brought the child back to the hospital for further evaluation. After hospital admission assessment, simultaneous presence of skin and scleral jaundice is noted. The girl had undergone an ultrasound examination, which revealed a mild 0.4cm dilation of the common bile duct (CBD) and suspected stones in both the CBD and gallbladder. The infant also presented with significant liver function abnormalities. After more than 2 weeks of symptomatic treatment including hepatoprotective therapy, there had been no significant improvement in the child's symptoms, signs, or liver function abnormalities. Subsequently, the girl was transferred to our hospital. The physical examination revealed the following parameters: temperature of 36.4°C, pulse rate of 123 beats per minute, respiratory rate of 30 breaths per minute, blood pressure of 92/56 mmHg, percutaneous oxygen saturation at 99%, and a weight of 5.9 kg. The infant exhibited severe jaundice without any accompanying skin rash or petechiae. Her stool appeared markedly clay-colored. No significant abnormalities were observed during the cardiac and pulmonary examinations. The abdominal examination revealed a flat abdomen with no signs of tenderness or rebound tenderness. No intra-abdominal masses were palpable. The Murphy's sign was negative. The laboratory results are presented with values as follows: bile acid (BA): 442.5 µmol/L, total bilirubin (TB): 267.8 µmol/L, conjugated bilirubin (CB): 205.7 µmol/L, alanine aminotransferase (ALT): 243 U/L, aspartate aminotransferase (AST): 436 U/L, γ-glutamyl transpeptidase (γ-GT): 1858 U/L, alkaline phosphatase (ALP): 304 U/L, blood amylase: 30 U/L, white blood cells (WBCs): 10.68×l0^9 /L, percentage of neutrophils: 15.9%, hemoglobin 87g/L and percentage of lymphocytes: 73.7%. Coagulation function test, routine urine, and stool values were within normal ranges. Furthermore, target cells were observed in the peripheral blood of this infant, and the proportion of reticulocytes was elevated (1.99%). An ultrasound examination was performed, revealing a 0.4cm diameter CBD with sedimentation. Liver fibro scan test showed significant elevation in liver stiffness (8.76kpa). Magnetic Resonance Cholangiopancreatography (MRCP) indicated suspected dilation and the presence of stones within CBD. Considering the severe biliary obstruction in the patient, ERCP is prioritized as the initial procedure. The infant was positioned prone and underwent ERCP under general anesthesia with intubation (endotracheal tube inner diameter 3.5mm). An Olympus JF-260V duodenoscope was employed for the procedure. The duodenal papilla exhibited a papillary appearance. Successful selective biliary cannulation was achieved using a two-lumen Dreamtome™ RX Cannulating Sphincterotome (Boston Scientific) and a 0.035-inch Dreamtome™ guide wire (Boston Scientific). Cholangiography was conducted from the upper to lower segments of the CBD. The CBD had a diameter of 0.4 cm at its widest part, displaying mild dilatation without evident significant contrast filling defects. No dilatation of the intrahepatic bile duct was observed. A longitudinal incision measuring 0.2 cm was made at the 11 o’clock position on the papilla of the bile duct. Multiple sediment-like stones were successively removed using a stone retrieval balloon (Cook Medical). Following the absence of bleeding, a 7 Fr straight-tip nasal biliary drainage catheter (Cook Medical) was inserted. The patient was transferred to the ward after the removal of the endotracheal tube, displaying stable vital signs. No post-operative complications occurred following the ERCP procedure. Laboratory results obtained one week after the ERCP procedure revealed the following values: bile acid (BA): 8.3 µmol/L, total bilirubin (TB): 66.8 µmol/L, conjugated bilirubin (CB): 56.1 µmol/L, alanine aminotransferase (ALT): 62 U/L, aspartate aminotransferase (AST): 61 U/L, γ-glutamyl transpeptidase (γ-GT): 540 U/L, alkaline phosphatase (ALP): 163 U/L, blood amylase: 48 U/L, white blood cells (WBCs): 12.41×l0^9 /L, percentage of neutrophils: 32.2%, and percentage of lymphocytes: 48.0%. Following ERCP and endoscopic nasobiliary drainage (ENBD), the girl's jaundice exhibited a marked improvement. She displayed increased energy levels and maintained a satisfactory food intake. One week post-ERCP, the nasal biliary catheter was removed, and liver function and stiffness (6.06kpa) had normalized within two weeks post-ERCP. Then the patient was discharged. Additionally, the child's hemoglobin level upon admission was 87g/L, with a elevated reticulocyte count and peripheral blood smear showing some target cells, suggesting a suspected diagnosis of hemolytic anemia. We also conducted tests for metabolic abnormalities in this patient. Her glucose-6-phosphate Dehydrogenase (G-6-PD) activity, blood tandem mass spectrometry, and urine gas chromatography showed no significant abnormalities. We also conducted whole-exome sequencing for the child and parents. The child's parents had no history of anemia or jaundice. The child carried heterozygous mutations in UGT1A1 and EPB41. There were two heterozygous mutation sites in UGT1A1, chr2:234669144 and chr2:234665659. One mutation came from the father, and both parents carried the other mutation. The mutation at chr2:234669144 may be related to transient familial neonatal hyperbilirubinemia, but its clinical significance remains unclear. Although EPB41 has been reported to be associated with elliptocytosis, the clinical significance of the EPB41 mutation site chr1:29344739 in the child remains unclear. Since the child quickly recovered after surgery, with the hemoglobin level returning to normal (recovery to 111g/L two months post-ERCP.) and no recurrence of jaundice during the six-month follow-up period at the time of this case report submission, we, after consultation with the parents, decided not to further investigate the cause of hemolysis in this patient.