Background & Aims: Single nucleotide polymorphisms (SNPs) in IL-10 gene promoter positions –1082, –819, and –592 and IL12B (30-UTR 1188-AC) gene 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 patients 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 test 87 patients with chronic hepatitis C (CHC) and 20 healthy control persons for IL-10 SNPs and IL-12B (30-UTR 1188-AC) SNP respectively. Group Ι include 48 patients who achieved SVR after receiving combined therapy (PegIFN) and RBV and group Π of 39 patients of non responders.Results: A significant difference (p<0.005) was observed in IL-10 _1082 GA showed significant difference in its genotype frequencies between responders and non-responders to therapy, where GG genotype had greater frequency in non- responders than GA and AA , While, IL-10_592AC and IL- 10 _819 SNP showed no significant difference. and in IL-12B genotype frequencies between responders and non-responders to interferon therapy, In responders CC genotype had greater frequency than CA and AA genotypes. Conclusion: SNP of IL10-1082 GG genotype is significantly associated with failure to response to PegIFN and RBV for patients with CHC infection genotype 4. IL12B gene at CC genotype is significantly associated with response. 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.