ObjectiveTo systematically review the combination of entecavir and interferon-α (IFN-α) in treating hepatitis B compared to entecavir alone. MethodsPubMed, EMbase, The Cochrane Library (Issue 12, 2013), Web of Science, CBM, CNKI, WanFang Data and VIP were searched for the randomized controlled trials (RCTs) on entecavir and interferon-α (IFN-α) in treating hepatitis B from inception to December 2013. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2.5. ResultsA total of 7 RCTs were finally included involving 543 cases. The results of meta-analysis revealed that, compared to entecavir alone, 24-week combined therapy was more effective in improving negative conversion rates of serum HBV-DNA (OR=2.93, 95%CI 1.79 to 4.79, P < 0.000 1), conversion rates of HBeAg (OR=2.36, 95%CI 1.35 to 4.14, P=0.003), and recovery rates of ALT (OR=2.73, 95%CI 1.73 to 4.32, P < 0.000 1). No statistical significance was found in terms of side effects. ConclusionCurrent evidence shows that combination of entecavir and IFN-α is more effective than entecavir alone in treating hepatitis B. Due to limited quality and quantity of the included studies, the abovementioned conclusion still needs to be verified by conducting more high quality studies.