Objective To explore the etiology, diagnosis, and treatment of Crigler-Najjar syndrome. Methods Clinical data of one pediatric patient with Crigler-Najjar syndrome was retrospectively analyzed. Results A 3-month-old boy was hospitalized for jaundice. His serum total bilirubin fluctuated between 450.1~479.3 μmol/L with majority being non-conjugated bilirubin. The phototherapy effect was poor. He was clinically highly suspected of Crigler-Najjar syndrome type I. Detection of locus mutation in Exon1 of uridine diphosphoglucuronyl transferase (UGT) 1A1  gene further confirmed Crigler-Najjar syndrome type I. Patient died in liver transplantation. Conclusions Crigler-Najjar syndrome is a type of genetic disorder of bilirubin metabolism and is caused by mutation in UTG1A1 gene leading to the complete or partial loss of its enzymatic activity. The diagnosis is mainly based on clinical features, laboratory examinations, and UGT1A1 gene detection. It can be cured by liver transplantation. Gene therapy is an ideal method for the ultimate cure.