BACKGROUND: In the clinic, pediatric acute necrotizing encephalopathy (ANE) primarily affects children under 5 years of age and is characterized by severe brain damage and high mortality. However, some challenges remain regarding the diagnosis and treatment of ANE. In the present study, we analyzed the clinical characteristics and related factors of ANE with the aim of providing improved diagnostic and treatment strategies. PURPOSE: The main purpose of this study is to gain a deeper understanding of the clinical characteristics and pathophysiology of ANE through a retrospective study, and to provide clinical practitioners with more effective. diagnostic and treatment strategies to improve patient survival rates and quality of life. METHODS: Thirty-four pediatric ANE patients admitted to Zhejiang University School of Medicine Hospital between February 2019 and December 2023 were included in this study. To identify the factors associated with mortality, clinical, laboratory and imaging data were analyzed with independent-sample t tests, Mann-Whitney U tests, Fisher exact probability tests and receiver operating characteristic curve analyses. RESULTS: In this cohort of 34 patients, the most common symptoms were fever, seizures, altered consciousness, vomiting, diarrhea and shock. The mortality rate was 55.9%. Laboratory tests revealed that patients who died had higher creatinine, lactate, activated partial thromboplastin time, thrombin time, interleukin (IL)-6, IL-10, creatine kinase, and D-dimer than survivors. Imaging examinations predominantly revealed symmetrical lesions in the thalamus. The fatal group displayed lower Glasgow Coma Scale (GCS) scores and severe complications. Other factors related to mortality included the arterial pH, GCS score and hospitalization duration. CONCLUSION: The most common symptoms of ANE are fever, seizures, altered consciousness, vomiting, diarrhea and shock, and ANE has a high mortality rate. The GCS score and arterial pH are critical biomarkers for assessing the severity of ANE.