Objective To evaluate the efficacy and safety of lamivudine combined with thymosin α1 therapy for patients with chronic hepatitis B.Methods Sixty-eight eligible patients with chronic hepatitis B were enrolled in this multi-center randomized controlled rlinical trial.Patients were randomized into the trial group and the control group(n=34 for each).Patients in trial group received thymosin α1 for 6 months and lamivudine for 12 menths:patients in control group received lamivudine for 12 months only.The rates of serum HBV DNA clearance.HBeAg loss,HBeAg seroconversion,ALT normalization and the safety of thymosin α1 were observed at 3rd.6th,12th and 18th month during and after the treatment.Results At 12th month of the treatment,there were significant differences in the rates of serum HBV DNA clearance,HBeAg loss and ALT normalization between two groups(χ2=31.17,7.17 and 5.92,P＜0.05);at 6th month after the treatment.there were significant differences in the rates of sernm HBV DNA clearance and HBeAg loss between two groups(χ2=4.53 and 7.17,P＜0.05).HBV DNA was not detected in 2 patients during 6-month follow-up study and no sever side effect was observed throughout the study.Conclusion The conlbination of lamivudine and thymosin α1 is safe and has better effect than the monotherapy of lamivudine in patients with chronic hepatitis B.