Recently, severe acute hepatitis with unknown etiology in children (SAHUEC) was emerging around the world. Since the first case was found in Scotland, at least 650 cases have been reported in 33 countries. The cases were sporadic, and few appeared to have an epidemiological link. Most children presented as acute hepatitis. In concerning an epidemiological pattern and clinical symptoms, the disease has been considered as an infection with unknown pathogen. Hepatitis A, B, C, D and E were excluded in all cases. Laboratory tests found that more than half of the children were positive for human adenovirus (HAdV), and HAdV-41 was identified in a portion of the cases, suggesting that there was an etiologic link between HAdV infection and SAHUEC. Currently two hypotheses are convincing, that are the adenovirus gene recombination and the altered viral tropism induced by cofactors. Particularly, a superantigen theory is more appealing, i．e. gastrointestinal adenovirus infection induces an onset of SARS-CoV-2 superantigen-mediated toxic shock and hepatocellular apoptosis. However, the true etiology still needs to be determined. This review intends to update available information regarding epidemiological investigation, etiological analysis, pathological alteration, laboratory examination, pathogenic detection, guidelines of diagnosis and treatment, as well as quarantine and preventive measures of SAHUEC, and to provide contemporary understanding of the underlying mechanisms for better therapy.