Background & Aims: Single nucleotide polymorphisms (SNPs) in IL-10 gene promoter positions –1082 (rs1800896), 819 (rs3021097), and –592 (rs1800872) and IL28B gene (rs12979860) in adults were shown to be associated with HCV clearance, In this study we aim to detect this association and the relation of these SNPs to treatment response prediction in Egyptian pediatric subjects with genotype 4 who received treatment with pegylated interferon (PegIFN) plus Ribavarin (responders and non-responders).Patients and Methods: A RFLP-PCR and Real time PCR techniques were used to genotype 54 pediatric patients with chronic hepatitis C (CHC) for IL-10 SNPs and IL-28B SNP respectively. Group 1 of 34 patients received combined therapy (PegIFN) and (RBV) for 24 weeks subdivided according to their response to treatment into responders and non-responders, and group 2 of 20 healthy subjects (control).Results: A significant difference (p<0.005) was observed in IL-28B rs12979860 genotype frequencies between responders and non-responders to interferon therapy, In responders CC genotype had greater frequency than CT and TT genotypes (60%, 30%, 10%) respectively with C allele in its wild genotype more likely to respond to treatment than in its mutant types. IL-10 _819 showed significant difference in its genotype frequencies between responders and non-responders to therapy, where TT genotype had greater frequency in responders that CT and CC (55%, 20%, 25%) respectively were the subjects with T allele (CT/TT) showed higher rates of response than those with no T allele (CC), its protective effect in both its recessive and dominant forms.Conclusion: SNP located 3 kb upstream of IL28B gene at (rs12979860) CC genotype as well as the IL-10 gene SNP at _819 TT genotype are significantly associated with response to PegIFN and RBV for pediatric patients with CHC infection genotype 4. These polymorphisms explain much of the difference in response between different genotypes and different alleles and can be used for predicting response to treatment before patient is prescribed to the expensive PegIFN-RBV therapy.