【Abstract】 Objective To explore the therapeutic efficacy and security of ombination therapy with interferon ( IFN) and a nucleoside analogue for treating chronic hepatitis B ( CHB).Methods 151 chronic hepatitis B patients were randomly divided into IFN group (48 cases), UC group (49 cases) and combination group (54 cases). The interferon was treated with interferon. The nucleoside analogues group was treated nucleoside analogues. The combination group was treated with interferon and nucleoside analogues. The hepatitis B E antigen (HBeAg) and hepatitis B virus gene (HBVDNA) level, the recovery rate of ALT and hepatitis B virus (HBV) antigen antibody after treatment 4, 12, 24 and 48 weeks were observed. Results The level of HBeAg and HBVDNA were declined after treatment, but the detection limit ratios of combined group was higher than the IFN group and UC group in 4, 12, 24 and 48 weeks after treatment(P＜005). The returned to normal rate of the 3 groups was statistically different. The recovery condition of the combination group was better than that of the other two groups(P＜005). The level of HBV antigen and antibody was significantly different of the 3 groups after treatment. Incidence of adverse reaction of 3 groups had no statistically significant difference (P＞ 005).Conclusions Combination therapy with interferon and a nucleoside analogue for treating chronic hepatitis B can increase the rate of HBeAg, HBV DNA and ALT returned normal. The therapeutic efficacy was better than exclusive using of IFN and NUC.