Abstract： Objective To evaluate the clinical efficacy and safety of bicyelol tablets in treatment of hepatitis B patients infected with YMDD mutation of HBV. Methods Sixty-eight chronic hepatitis patients infected with HBV YMDD mutants and 100 patients with non-mutants HBV were enrolled in the study. All patients received bicyclol tablets orally 150 mg/d, t. i. d, for 24 weeks. Clinical symptoms, signs and adverse effects were observed, and the blood routine, liver function tests, serum HBV markers and HBV DNA loads were examined at 12th and 24th week of the study, Results After treatment for 24 weeks, the normalization rates of ALT and AST in mutant group were 79.4% ( 54/68 ) and 70. 6% (48/68) ; 11 ( 16. 2% ) patients were markedly effective and 14 (20. 6% ) were effective. Clearance rates of HBeAg and HBV DNA were 27.9% ( 17/61 ) and 17.6% ( 12/68 ), while the seroconversion rate of HBeAg was 14. 7% (9/61). The differences of the above indexes were not statistically significant between mutant group and non-mutant group. Conclusion Bicyciol can both protect liver functions and inhibit virus replication in patients infected with HBV YMDD mutants.