〔Abstract〕 Objective To investigate the clinical effect of Ganshuang granule combined with entecavir in the treatment of chronic hepatitis B cirrhosis. Methods A total of 60 patients with chronic hepatitis B cirrhosis treated in Xinxiang Infectious Disease Hospital from August 2019 to August 2021 were selected and divided into a control group and an observation group by random number table method, with 30 cases in each group. The control group was treated with entecavir, and the observation group was treated with Ganshuang granule on the basis of the control group. The treatment time of the two groups was 6 months. The clinical efficacy after treatment, related cytokines, liver fibrosis, liver function and hepatitis B virus replication condition before and after treatment were compared between the two groups. Results The total effective rate of the observation group was 96.67 %, higher than 80.00 % of the control group, and the difference was statistically significant (P < 0.05). After treatment, the serum levels of interleukin-17 (IL-17), IL-35, T regulatory cell (Treg) and IL-23 in the two groups were decreased to varying degrees, and the serum levels of IL-17, IL-35, Treg and IL-23 in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.05). After treatment, the levels of serum hyaluronic acid (HA), laminin (LN), type Ⅲ procollagen (PCⅢ) and type Ⅳ collagen (IV-C) in the two groups decreased to varying degrees, and the levels of HA, LN, PCⅢ and IV-C in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.05). After treatment, the levels of serum albumin (ALB) of the two groups were increased to varying degrees, serum total bilirubin (TBIL) and hepatitis B virus deoxyribonucleic acid (HBV-DNA) levels were decreased to varying degrees, and after treatment, serum ALB level of the observation group was higher than that of the control group, serum TBIL and HBV-DNA levels were lower than those of the control group, the differences were statistically significant (P < 0.05). Conclusion Ganshuang granule combined with entecavir in the treatment of chronic hepatitis B cirrhosis can effectively reduce the inflammatory response of patients, enhance immune ability, improve liver function, delay the progression of liver cirrhosis, inhibit the replication of hepatitis B virus and improve the therapeutic effect.