Abstract: Objective To explore the efficacy and safety of different treatment regimens in patients with pulmonary tuberculosis combined with hepatitis B, and to provides an objective evidence for the choice of treatment regimens. Methods A prospective cohort study was used to select 126 patients of tuberculosis combined with hepatitis B in our hospital from January, 2016 to January, 2017, according to the random number table, the subjects were randomly divided into A (control) group, B (lamivudine group) and C (entente Cave) group, 42 cases in each group for 6 months according to different treatments, the liver function, HBV DNA negative conversion rate, the effect of pulmonary tuberculosis and the occurrence of adverse reactions were observed in all groups, and the data were analyzed by SPSS 21.0 statistics software. Results After 6 months of treatment, the level of ALT, AST and TBIL in group B and C was significantly lower than that in group A (P<0.05). The ALT and TBIL levels of C group were lower than that of B group (P<0.05). The absorption of chest lesions and the rate of HBV DNA turned negative conversion rate in group C were significantly higher than those in the A group (P<0.05), the incidence of total adverse reactions in group B and C was lower than that in group A (P<0.05). Conclusion The anti-tuberculosis regimen combined with lamivudine and entecavir has a certain advantage in reducing the liver damage and protecting the liver function of anti-tuberculosis drugs. It may be more beneficial to the treatment effect of anti-tuberculosis drugs on the premise of normal liver function. The indexes of liver function and HBV DNA negative conversion rate in entecavir group were better than those in lamivudine group, and the safety of the two drugs is acceptable.