Objective To study the efficacy of thymosin α1 in the treatment of chronic hepatitis B virus( HBV) infection with low viral load. Method Seventy- six patients with low- viral load chronic HBV infection admitted to our hospital from June 2011 to June 2013 were randomly assigned to treatment group,and forty- one patients were assigned to control group. The treatment group received subcutaneous injection of 1. 6 mg thymosin α1 twice a week,and the treatment stopped at 3 months if the patients were negative for serum HBV DNA; otherwise,the treatment was extended to 6 months. The control group did not receive any treatment. The serum HBV DNA clearance rates at months 3 and 6 of treatment were measured in both groups. Comparison of continuous data between two groups was made by t test,and comparison of categorical data was made by χ2test. Results The treatment group showed significantly higher HBV DNA clearance rates than the control group at months 3 and 6 of treatment( χ2= 10. 61,P < 0. 01; χ2= 13. 09,P < 0. 01). At month 6 in the treatment group,the HBV DNA clearance rate in patients who had HBV DNA < 104 copies / ml and were positive for HBe Ag showed no significant difference from that in those who were negative for HBe Ag( χ2= 0. 02,P > 0. 05),but was significantly higher than that in patients with HBV DNA ≥104copies / ml( χ2= 7. 52,P < 0. 01). Conclusion Thymosin α1 significantly promotes HBV DNA clearance in patients with low- viral load chronic HBV infection. The clearance rate is negatively correlated with the DNA load,but shows no correlation with the HBe Ag status.