Hepatitis C virus (HCV) infection is a major health problem throughout the world. Last estimates indicate that 175 million people are infected. Egypt has the highest worldwide prevalence of HCV (10-20%). HCV causes a chronic infection that can result in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Predictor of response to therapy with pegylated interferon (PEG-IFN) plus ribavirin (RBV) serve as decision tools for physicians to identify patients who are likely or unlikely to achieve sustained virological response (SVR) and to consider pre-treatment counseling in those patients with a reduced likelihood of successful therapy, perhaps sparing them the side effects and cost of therapy. Single nucleotide polymorphisms (SNPs) in the gene that encodes interleukin IL28B predict response of patients with chronic hepatitis C to antiviral therapy. We investigated the role of polymorphism IL28B rs8099917 on SVR of treatment of HCV infected Egyptian naïve patients. Our study was conducted on 153 Egyptian patients infected with HCV who treated with pegylated interferon α plus ribavirin. Successful treatment was ascertained based on SVR . Genotyping of rs8099917 polymorphisms near the IL28B gene was performed. Patients were grouped to TT, TG and GG. IL-28B genotypes (rs8099917) were analyzed for association with treatment response. We have demonstrated that carriers with the TT genotype are more likely to achieve SVR. We found that the rate of SVR was significantly higher near three times response (73.3% vs. 26.7%, p = 0.002) in patients with the IL28B major allele (TT, wild type) compared to those with the minor allele (non TT, mutant type). In conclusion, IL28B gene polymorphism was significant pre-treatment predictors of response to PEG-IFN/RBV in chronically infected Egyptian patients with HCV. Analysis of IL-28B genotype might be used to guide treatment for these patients particularly in the context of emerging therapies and direct-acting antiviral agents.