Abstract: OBJECTIVE To explore the relationship between the single nucleotide polymorphisms (SNPs) of IL28B gene and the serum levels of IFN-λ3 with polyethylene glycol interferon combined with ribavirin treatment to chronic hepatitis B patients. METHODS A total of 100 HBeAg positive patients with chronic hepatitis B in our hospital from Jun. 2013 to Dec. 2013 were selected and treated with peg-interferon α-2a (Peg-INF-α) combined with ribavirin. After 48 weeks of treatment,all the patients were divided into responsive group( n=48) and non-responsive group(n=52).The relationship among IL28B polymorphisms, HBV genotype, hepatitis B s antigen(HBsAg) levels , HBeAg levels,IFN-λ3 levels and the response to the treatment were analyzed. RESULTS The distribution frequencies of IL28B rs 12979860 CC and CT+TT genotypes showed significant differences between the responsive group and nonresponsive group (χ²=8.253,P<0.05). The levels of HBV-DNA、HBsAg and HBeAg for 48 weeks in responsive group were significantly lower than nonresponsive group, and the difference was statistically significant (P<0.05).The levels of IFN-λ3 for 48 weeks in responsive group were significant higher than nonresponsive group (P<0.05). The levels of IFN-λ3 of IL28B polymorphisms CC genotype were significantly higher than CT+TT genotype (P<0.05). CONCLUSION The levels of IL28B SNPs and IFN-λ3 would be possible to influence the response of peg- interferon α-2a combined with ribavirin, which has certain predict value for the treatment in CHB patients.