Abstract: OBJECTIVE To explore the effects of Epstein-Barr virus (EBV) infection on liver function and prognosis in patients with chronic hepatitis B (CHB). METHODS Sixty CHB patients with EBV and HBV infection who were admitted to Henan People's Hospital from Feb. 2016 to Feb. 2019 were enrolled as the test group. CHB patients only with HBV infection who were admitted during the same period were enrolled as the control group. The clinical data, changes in liver function and disease progression were compared between the two groups. The risk factors for disease progression in CHB patients were analyzed. RESULTS The hospitalization time, proportion of severe patients, levels of WBC and EBV DNA in test group were significantly higher than those in the control group (P<0.05), while proportions of serum albumin, Hb, PTA, CD₈⁺T lymphocytes and NK cells were significantly lower than those in control group (P<0.05). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), indirect bilirubin (IBIL), direct bilirubin (DBil), GGT and ALP globulin (GLB) in the test group were significantly higher than those in the control group (P<0.05). There were 23 cases (38.33%) with disease progression into cirrhosis in the test group, which was significantly more than that in the control group of 13 cases, accounting for 21.67% (χ²=3.968, P=0.046). Kaplan-Meier survival curve analysis showed that there was no significant difference of the progression-free survival (PFS) rate in CHB patients between the test group and control group (Log-rank t=2.61, P= 0.106). Multivariate Logistic regression analysis showed that ALT≥150 U/L, drinking and family history of hepatitis B were risk factors for disease progression into cirrhosis in CHB patients (P<0.05). CONCLUSION The liver function damage in CHB patients with EBV and HBV infection is more severe than that in CHB patients with HBV infection, and the possibility of disease progression into cirrhosis is higher.