OBJECTIVE： To compare the effects and medication cost of tenofovir disoproxil and entecavir in the treatment of hepatitis B. METHODS： A total of 300 patients with HBV infection selected from our hospital during Sept. 2015-Sept. 2016 were randomly divided into tenofovir disoproxil group and entecavir group， with 150 cases in each group. Tenofovir disoproxil group was given Tenofovir disoproxil fumarate tablet 300 mg orally， qd. Entecavir group was given Entecavir tablet 0.5 mg orally， qd， for consecutive 48 weeks. HBV-DNA level， negative conversion rate of HBV-DNA， ALT level and ALT normalization rate were compared between 2 groups before treatment， after 24， 48 weeks of treatment. The medication cost-effectiveness ratio and ADR were compared between 2 groups after 48 weeks of treatment. RESULTS： There were no statistical significances in the level of HBV-DNA between 2 groups before treatment， the level of ALT and ALT normalization rate before treatment， after 24， 48 weeks of treatment （P＞0.05）. Compared with entecavir group， the level of HBV-DNA in tenofovir disoproxil group after 24， 48 weeks of treatment was decreased significantly （P＜0.05）； the negative rate of HBV-DNA in tenofovir group was slightly higher after 24 weeks of treatment， without statistical significance （P＞0.05）； the negative rate of HBV-DNA was slightly increased after 48 weeks of treatment （P＜0.05）. Negative conversion rate of HBV-DNA and medication cost-effectiveness ratio of ALT normalization in tenofovir disoproxil group were better than entecavir group （P＜0.05）. The incidence of ADR in tenofovir dipivoxil group was lower than entecavir group （P＜0.05）. CONCLUSIONS： Tenofovir dipivoxil can effectively treat HBV， and its effects and medication cost are both better than entecavir.