Egypt has a high prevalence of hepatitis C virus (HCV) infection in children. Limitations of the current HCV treatment are low rate of sustained virological response (SVR) approximately 50%, significant side effects and high expenses, making prediction of treatment response crucial.This study aimed to investigate association of single nucleotide polymorphisms (SNPs) in IL10, IL28B and IL29 genes in predicting treatment response in HCV infected children.Methods: Seventy three Egyptian pediatric patients, receiving pegylated interferon α 2b (PEG-IFN α 2b) and ribavirin were included, for whom liver biopsy was performed for evaluation of fibrosis score. Genotyping of SNPs in IL10 gene (rs1800896, rs302109, and rs1800872), IL28B gene (rs12979860, rs8099917) and IL29 gene (rs30461) as well as HCV genotype were analyzed by Real-time PCR.Results: The CC genotype (IL28B; rs12979860) had 6.62 folds higher chance to develop SVR than CT and TT genotypes (p =0.004). The G allele (SNP rs8099917; IL28B), was 2.257 times more likely to be resistant to HCV therapy than the protective T allele (P= 0.04). The CC/TT IL28B haplotype had 6.632 times more chance to respond to HCV therapy compared to other haplotypes (P= 0.008).Other host factors such as, lower pretreatment PCR levels, higher pretreatment serum GGT levels, and lower degrees of hepatitis activity index (HAI) showed significantly higher SVR, (P= 0.005), (p= 0.001) and (p=0.004) respectively.In multivariate analysis, IL28 gene SNP rs12979860, IL10 gene SNPs -592 A>C and basal viral load were independent variables that significantly improved independent prediction of response to HCV therapy. Conclusions: Genetic variation in IL28B and IL10 -592 A>C is associated with response to HCV treatment. This association can be translated into clinical decision making for HCV treatment.