OBJECTIVE： To observe therapeutic efficacy and safety of entecavir combined with long-acting interferon in the treatment of HBeAg positive chronic hepatitis B （CHB）. METHODS： A total of 140 patients with HBeAg positive CHB selected from our hospital during May 2013-May 2015 were divided into observation group and control group according to random number table， with 70 cases in each group. Both groups received routine liver-protecting treatment； control group was additionally given Peginterferon α-2b injection 80 μg subcutaneously， once a week； observation group was additionally given Entecavir dispersible tablets 0.5 mg， po， qd， on the basis of control group. Both groups received treatment for consecutive 50 weeks. Clinical efficacies， liver function indexes before and after treatment， virological efficacies and the occurrence of ADR of 2 groups were observed. RESULTS： Each 5 cases withdrew from the study in 2 groups， and 130 cases （65 cases in each group） completed the study. Total response rate of observation group was 90.8％， which was significantly higher than 76.9％ of control group， with statistical significance （P＜0.05）. Before treatment， there was no statistical significance in the levels of ALT， AST， ALB or TBIL between 2 groups （P＞0.05）. After treatment， the levels of ALT， AST and TBIL in 2 groups were decreased significantly， while ALB level was increased significantly， the observation group was significantly better than the control group， with statistical significance （P＜0.05）. After 50 weeks of treatment， the negative conversion rate of HBV-DNA， HBeAg serology conversion rate and ALT normalizing rate of observation group were significantly higher than those of control group， and virologic breakthrough rate was significantly lower than control group， with statistical significance （P＜0.05）. No severe ADR was found in 2 groups. There was no statistical significance in the incidence of ADR （P＞0.05）. CONCLUSIONS： The entecavir combined with long-acting interferon show definite therapeutic efficacy for HBeAg positive CHB， inhibit the replication of HBV and improve liver function of patients with good safety.