Abstract: OBJECTIVE To explore the characteristics of liver function indexes and levels of related cytokines such as serum IL-22 in patients with cirrhosis overlapping hepatitis E virus (HEV) infection and observe the value of serum IL-22 in judgment of severity of disease. METHODS A total of 96 patients with acute HEV infection who were treated in the hospital from May 2010 to May 2015 were recruited as the study objects and divided into the superinfection infection group with 57 cases and the single infection group with 39 cases according to the status of HBV-related cirrhosis, meanwhile, 30 healthy volunteers who received the physical examination were assigned as the control group, and 10 decompensated cirrhosis patients without acute HEV infection were set as the blank group.The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), white blood cell (WBC), platelet (PLT), creatinine (Cr), and prothrombin activity (PTA) of the subjects were determined; the levels of cytokines such as IL-22, IL-17, IL-6, TNF-α, and IFN-γ were determined by means of enzyme-linked immunosorbent assay; the indexes were observed and compared among the groups. RESULTS The levels of ALT, AST, and TBIL of the superinfection group were significantly higher than those of the single infection group (P＜0.05).The levels of coagulation function indicators such as ALB, PTA, and PLT of the superinfection group were significantly lower than those of the single infection group (P＜0.05).The IL-22 level of the patients with superinfection was significantly higher than that of the patients with single infection and the patients in the blank group (P＜0.05).The levels of IL-17 and TNF-α of the superinfection group were higher than those of the blank group, the levels of IL-17 and TNF-α of the blank group were higher than those of the single infection group (P＜0.05).There was no significant difference in the level of serum IFN-γ among the groups. CONCLUSION The HBV-related cirrhosis complicated with HEV superinfection may result in more severe liver injury, and the IL-22 may involve in the process of the hepatic inflammatory injury after the HEV infection.