Objective To investigate the clinical efficacy of combined therapy of Gankang Granule and Entecavir for patients with chronic hepatitis B. Methods A total of 118 patients with chronic hepatitis B treated between January 2012 and January 2013 were randomly divided into treatment group (n=59) and control group (n=59). Patients in the treatment group were treated with Gankang Granule and Entecavir, while those in the control group were treated with Entecavir alone. Results Before treatment, there was no significant difference between the two groups in such liver fibrosis evaluation indexes as hyaluronic acid (HA), laminin (LN), procollagenⅢ(PCⅢ), and collegen typeⅣ(CⅣ) (P > 0.05). After treatment, the two groups had significant differences in HA, LN, PCⅢ, and CⅣ(P < 0.05). After 48 weeks of treatment, the alanine aminotransferase recovery rate was significantly different between the two groups (P < 0.05); but there was no significant difference in hepatitis B virus DNA negative conversion rate, hepatitis B e antigen negative conversion rate and hepatitis B e antibody seroconversion rate (P > 0.05). Forty-eight weeks after treatment began, 45 patients underwent liver biopsy which showed that liver fibrosis alleviation was significantly better in the treatment group than the control group (P < 0.05). Conclusions Gankang granule combined with antiviral drug Entecavir for chronic hepatitis B is better in protecting the liver and alleviating hepatic fibrosis than the sole Entecavir. The combined method is worthy of being promoted.