OBJECTIVE： To observe clinical efficacy and safety of individual antiviral therapy of tenofovir combined with interferon α1b for chronic hepatitis B （CHB）. METHODS： 96 CHB patients were randomly divided into control group， observation group A and observation group B， with 32 cases in each group. Control group was given entecavir orally， 0.5 mg， qd； observation group A was given tenofovir orally， 1 piece， qd； observation group B was additionally given interferon α1b， 50 μg， 3 times a week， on the basis of observation group A. The treatment course lasted for 48 weeks in 3 groups. Clinical efficacy of 3 groups was compared， and the changes of serum liver function indexes， HBV-DNA negative conversion rate and the occurrence of ADR were compared before and after treatment. RESULTS： The total effective rate of observation group B （84.38％） was significantly higher than that of observation group A （62.60％） and control group （37.50％）， and that of observation group A was significantly higher than control group， with statistical significance （P＜0.05）. Compared with before treatment， the serum levels of AST， ALT and TBIL were significantly decreased after treatment in 3 groups； the observation group B were significantly lower than those of observation group A and control group， with statistical significance （P＜0.05）； there was no statistical significance between observation group A and control group （P＞0.05）. The negative rate of HBV-DNA in observation group B were significantly higher than those in control group and observation group A after 12 and 24 weeks of treatment， with statistical significance （P＜0.05）； there was no statistical significance between observation group A and control group （P＞0.05）. No obvious ADR was found in 3 groups. CONCLUSIONS： Tenofovir combined with interferon α1b shows significant clinical efficacy for CHB， and is significantly better than that of entecavir and tenofovir alone.