Abstract: Objective To investigate the clinical features of pediatric liver failure and provide reference for its diagnosis, prevention, and treatment. Methods Pediatric patients who were diagnosed with liver failure at Nanjing Children's Hospital from February 2012 to February 2023 were selected and their clinical data were analyzed. Results This study included 105 children with liver failure. Their age ranged from 1 month and 1 day to 14 years and 11 months, with a median of 21 months. There were 67 males and 38 females, and 82.8% were diagnosed with acute or subacute liver failure. The etiologies included genetic metabolic diseases in 24 cases (22.9%), infectious factors in 12 cases (11.4%), and biliary diseases in 10 cases (9.5%), while 34.3% had unknown causes. The most common clinical manifestations were poor appetite, fever, and jaundice. Major complications included hepatic encephalopathy, electrolyte imbalance, and infections. No statistical differences were found between the survival group and the mortality group in terms of age, albumin, blood ammonia, presence of hepatic encephalopathy, alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) (P>0.05). However, the survival group showed decreases in the Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) scores, total bilirubin levels, and international normalized ratio (INR), as well as increases in platelet counts, compared with the mortality group (P<0.05). Conclusions Genetic metabolism, infections, and biliary diseases are common causes of pediatric liver failure, with genetic metabolic disorders being the most prevalent, particularly hepatolenticular degeneration. MELD/PELD scores can predict the prognosis of liver failure. Clinical feature analysis and MELD/PELD scores can further guide the diagnosis, treatment, and prognosis of pediatric liver failure.