Abstract： Acute necrotizing encephalopathy（ANE）causes a very high mortality rate in children.However，the pathogenesis of ANE is still unclear，so no better treatment is available.Recent studies have shown that cytokine storms，genetic susceptibility，and mitochondrial dysfunction are key factors in the pathogenesis of ANE.It is now acknowledged that cytokine storms mediated by interleukin-6 and tumor necrosis factor-α are key factors in the pathogenesis of ANE in children.Genetic susceptibility due to genetic mutations plays an indirect role，and children with genetic mutations are more likely to develop ANE after exposure to influenza viruses.Mitochondrial dysfunction interacts with cytokines and gene mutations to jointly promote the development of ANE，but the exact mechanisms are unknown.We hope a deeper understanding of the pathogenesis of ANE will be achieved in the future.Therefore，the therapeutic regimens for ANE will be developed to limit the disease progression and to reduce the rate of disability and mortality in children.