Acute necrotizing encephalopathy (ANE) is a rare disease in childhood. We reviewed the 10-year data from a local pediatric department, reported the clinical characteristics, laboratory tests, neuroimaging findings, and outcome of the acute necrotizing encephalopathy cases and identified the potential factors affecting the outcome. Eight episodes of acute necrotizing encephalopathy among 7 patients were recorded, in which all of them had an initial presentation of fever and seizure. We identified that acute necrotizing encephalopathy patients with a severe score of Glasgow Coma Scale (GCS) on presentation, brainstem involvement in magnetic resonance imaging (MRI) of the brain, and higher MR imaging scores were associated with worse outcome. Association of outcome with acute necrotizing encephalopathy severity score, platelet count, and serum alanine aminotransferase level did not reach a statistically significant level. These results highlight the importance of combined clinical, laboratory, and neuroimaging findings in determining the prognostic outcome of acute necrotizing encephalopathy patients.