Objective To systematically review the effectiveness and safety interferon-α (IFN-α) combined with lamivudine vs. IFN-α alone in treating children with Hepatitis B. Methods Such databases as The Cochrane Library, PubMed, EMbase, Web of Science, CBM, CNKI, VIP and WanFang Data were electronically searched for randomized controlled trials (RCTs) on IFN-α combined with lamivudine in treating children with hepatitis B. Two reviewers screened literature, extracted data, and assessed the methodological quality of the included studies. Then, meta-analysis was performed using RevMan 5.0 software. Results 8 RCTs were included, with comparable baseline. The results of meta-analysis showed that, compared to the IFN-α alone group, the combined therapy group had higher negative rates of serum HBV-DNA and HBeAg. There was no significant difference in the positive rate of anti-Hbe and the incidence of adverse reaction between the two groups. Conclusion Current evidence shows that IFN-α combined with lamivudine was more effective than IFN-α alone in treating children’s hepatitis B.