Objective To evaluate the efficacy and safety of genus Phyllanthus for chronic HBV infection. Design a systematic review of randomized clinical trials. Methods Randomized trials comparing genus Phyllanthus versus placebo, no intervention, general non-specific treatment, other herbal medicine, or interferon treatment for chronic HBV infection were identified by electronic and manual searches. Trials of Phyllanthus herb plus interferon versus interferon alone were also included. No blinding and language limitations were applied. The methodological quality of trials was assesses, by the Jadadscale plus allocation concealment. Results Twenty-two randomized trials (n=1 947) were identified. The methodological quality was high in five double blind trials and rest was low. The combined results showed that Phyllanthus species had positive effect on clearance of serum HBsAg (relative risk 5.64, 95%C1 1.85 to 17.21) compared with placebo or no intervention. There was no significant difference on clearance of serum HBsAg, HBeAg and HBV DNA between Phyllanthus and interferon. Phyllanthus species were better than non-specific treatment or other herbal medicines on clearance of serum HBeAg, HBeAg, HBV DNA, and liver enzyme normalization. Analyses showed a better effect of the Phyllanthus plus interferon combination on clearance of serum (1.56, 1.06 to 2.32) and HBV DNA (1.52, 1.05 to 2.21) than interferon alone. No serious adverse events were reported. Conclusions Based on the review Phyllanthus species may have positive effect on antiviral activity and liver biochemistry in chronic HBV infection. However, the evidence is not b due to the general low methodological quality and the variations of the herb. Further large trials are needed.