Objective: Seasonal influenza associated neurological complications had high mortality and morbidity rates in children. In this study, we aimed to investigate the clinical characteristics and mortality risk factors in children with influenza-associated encephalopathy. Methods: Retrospectively analyze the clinical data, laboratory tests, and imaging examinations of 68 children diagnosed with influenza-associated encephalopathy from January 2016 to December 2019 at Guangzhou Women and Children’s Medical Center, and the cases were divided into survival and non-survival groups by disease outcome and analyzed between two groups Results: Among the 68 children with influenza-associated encephalopathy, 40 were male, and 28 were female, aged from 3 months to 13 years, of which 66.18% (45/68) were under 5 years old. Pathogenetic tests showed that influenza virus type A accounted for 63.24% (43/68), and influenza virus type B accounted for 36.76% (25/68). Typical brain MRI changes in childhood influenza-associated encephalopathy were bilateral symmetrical lesions of the thalamus, basal ganglia, brainstem, and cerebellum. 68 patients had a mortality rate of 20.59% (14/68), with a significantly higher proportion of fever peak >39°C, Acute Disturbance Of Consciousness (ADOC), and cardiac arrest in the non-survival group than in the survival group (P<0.05). Laboratory tests showed significantly higher Alanine Aminotransferase (ALT), Aspartate Transaminase (AST), Creatinine Kinase (CK), and Lactate Dehydrogenase (LDH), Lactate, C-Reactive Protein (CRP), and CSF protein levels in the non-survival group compared with the survivor (P<0.05), and among them, elevated ALT, AST, LDH, and CSF protein were independent high-risk factors for death from influenzaassociated encephalopathy. Conclusions: Children under 5 years of age with influenza are prone to combine neurological complications and have a higher mortality rate. Significant elevations in ALT, AST, LDH, and CSF proteins predict death from influenzaassociated encephalopathy in children.