Abstract：Objective：To observe the effect of Shenqi Yigan Decoction combined with Entecavir on liver hardness and serum cytokeratin 18 （CK18） levels in patients with hepatitis B cirrhosis. Methods：A total of 80 cases of patients with compensated hepatitis B cirrhosis admitted to the General Hospital of Yima Coal Industry Group Co.， Ltd. from June 2022 to June 2023 were randomly divided into the control group and the observation group， with 40 patients in each group. The control group was treated with Entecavir， while the observation group was treated with Shenqi Yigan Decoction in addition to the treatment of the control group. After six months of treatment，the clinical efficacy， liver hardness， laboratory indicators [CK18， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）]，and liver function [total bilirubin （TBil），aspartate aminotransferase （AST），and alanine aminotransferase （ALT）] levels were observed and compared between the two groups. Results： The total effective rate was 97.50% （39/40） in the observation group， while that of 80.00% （32/40） in the control group， the difference being significant （P＜0.05）. After treatment， the liver hardness in both groups were decreased when compared with those before treatment （P＜ 0.05）， and the liver hardness in the observation group was lower than that in the control group （P＜0.05）. After treatment， the levels of serum CK18， IL-6， and TNF-α in both groups were decreased when compared with those before treatment （P＜0.05），and the levels of these three indicators in the observation group were lower than those in the control group （P＜0.05）. After treatment，the levels of serum TBil，AST，and ALT in both groups were decreased when compared with those before treatment，and the levels of these three indicators in the observation group were lower than those in the control group （P＜0.05）. Conclusion：The combination of Shenqi Yigan Decoction and Entecavir can effectively reduce the liver hardness of patients with hepatitis B cirrhosis， inhibit the body's inflammatory response， reduce liver damage，improve liver function，and has better therapeutic effects than simple western medicine treatment.