BACKGROUND : Polymorphisms near the interferon lambda 3 (IFNL3, also known as IL28B) have been proposed to be associated with interferon (IFN)-induced hepatitis C virus (HCV) clearance, but the impact of IFNL3 variations on the result of IFN-based therapy in chronic hepatitis B (CHB) infection is still poor understood. METHODS : The purpose of this study was to evaluate the relationship between the IFNL3 polymorphisms and the effectiveness of IFN therapy in patients infected with CHB by means of meta-analysis. PubMed and Embase were utilized to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were analysed together to assess the strength of the association. Subgroup analysis was mainly performed according to HBeAg. RESULTS : Twelve studies of 1645 CHB patients met the inclusion criteria and were selected in our meta-analysis. One polymorphism, rs12979860, near to the IFNL3 gene had significant association with the response of CHB patients to IFN-based therapy (OR = 2.35, 95% CI: 1.61-3.42 in allelic model). Another polymorphism, rs8099917, had a similar result (OR = 1.57, 95% CI: 1.03-2.40 in dominant model; and OR = 1.88, 95% CI: 1.21-2.90 in allelic model). When stratified by HBeAg, the antiviral outcome was markedly influenced by both two SNPs in HBeAg positive group (for rs12979860, OR = 1.90, 95% CI: 1.31-2.76 and OR = 2.07, 95% CI: 1.26-3.41 in dominant and allelic models respectively; for rs8099917, OR = 1.67, 95% CI: 1.04-2.67 in dominant model and OR = 1.77, 95% CI: 1.10-2.85 in allelic model). CONCLUSIONS : We concluded that two polymorphisms (rs12979860 and rs8099917) of IFNL3 may play a crucial role in the IFN-based treatment of CHB, especially in HBeAg positive group.