Abstract: OBJECTIVE To investigate the cortisol, immune indexes and prognosis in patients with HBV and HEV related acute on chronic liver failure, so as to provide references for clinical research. METHODS A total of 68 patients with HBV infection causing ACLF (HBV group) and 59 patients with HBV overlapping combined HEV infection causing ACLF (overlapping group) were selected from Mar. 2012 to Nov. 2015. Fasting venous blood was extracted for the detection of peripheral blood cortisol, γ-interferon, IP-10 level and liver function indexes. The survival situation were analyzed followed up for 6 months, and the factors influencing prognosis were analyzed. RESULTS The cortisol level in overlapping group was lower than that in HBV group. The γ-interferon and IP-10 levels in overlapping group were higher than those in HBV group. The differences were significant (P<0.05). There were 29 patients in overlapping group were died followed up for 6 months, which were higher than 15 in HBV group. The difference was significant (P<0.05). CONCLUSION The clinical features of patients with superinfection of HEV and HBV related ACLF were more serious.The higher level of MELD score and Child-Pugh score and the lower level of PTA,the worse prognosis.