The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest number of infections reported in Egypt. BCL-2 gene polymorphism at codon 43 (127G/A) has been found to be a reliable and sensitive marker for the prediction of response to interferon therapy during viral infections. This study examined the correlation of BCL-2 gene polymorphism with the response to treatment with pegylated-IFN-alfa2b and ribavirin. Eighty patients with type 4 HCV and 40 healthy volunteers as controls were enrolled in a prospective study. Quantification of HCV-RNA by real-time PCR was performed for every patient, and gene polymorphism of BCL-2 (ala 43 Thr) was performed for all patients and controls. There was a statistically significant difference between non-responder patients and control group as regards the 43 Thr genotype and allele (P<0.05). Also, there was a statistically significant difference between responders and non-responders (P<0.05) as regards 43 Thr genotype and alleles. We conclude that BCL-2 gene polymorphism at codon 43 (127G/A) is a new biological marker to potentially identify responders and non-responders of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN in combination with ribavirin.