Background: The World Health Organization has declared HCV as a global health problem, with approximately 3% of the world’s population infected with HCV with considerable regional variations. Prediction of treatment response in patients with chronic HCV infection is a crucial issue particularly with the current poor response rate, high cost and many side effects of therapy. One of the modifiable host factors influencing the response to treatment may be the emergence of anti-interferon antibodies (anti-IFN Abs) during treatment. This may cause no response or relapse in HCV patients. These antibodies may also inactivate the native interferon alpha protein in these patients.Aim of the work: To identify the role of genomic interferon alpha 2 alleles and anti-IFN Abs in the response to treatment of chronic hepatitis C patients with pegylated interferon (PEG-IFN) alpha and ribavirin.Methods: Retrospective study conducted on 220 chronic hepatitis C patients who had already received combined PEG-IFN alpha, divided into 4 groups according to type of rhIFN-α2 given (either PEG-IFN alpha 2a or 2b), and according to treatment's response (either end of treatment response or no response). These patients groups were screened for endogenous IFN alpha 2 alleles and presence of anti-IFN Abs. Additional 25 healthy subjects were screened to identify the predominant type of native IFN alpha 2 alleles and presence of anti-IFN Abs, among them.Results: Results have shown that, IFN-α2b was the only allele detected in the genomic DNA of all cases under study which indicates that there is no influence for the type of endogenous interferon alpha 2 alleles on the response to combined PEG-IFN and ribavirin therapy. However, the incidence of development of these antibodies was 14/96 (14.58%) in responders and 35/85 (41%) in non responders. Statistically significant higher levels of anti-IFN Abs had been found between all HCV patients received treatment compared to control group, between patients received PEG-INFα2a compared to those received PEG-INFα2b and finally between non responders compared to responders in each drug group. It could be suggested that, the development of antibodies to rhIFN-α2 could influence the virological response to IFN treatment in chronic HCV infection. No significant correlation had been found between the incidence of anti-IFN Abs development and other clinical, laboratory or histopathological data of the patients.