Background: Epstein Barr(EBV) is a ubiquitous pathogen that infects the majority of humans. Coinfection of EBV and hepatitis C virus (HCV) may worsen the prognosis of HCV-infected patients. Aim: This study was conducted to examine the role of EBV reactivation in determining the response rate to treatment with interferon and ribavirin therapy in chronic HCV patients. Patients and Methods: One hundred patients with proven chronic hepatitis C who underwent PEG IFN + ribavirin therapy and twenty healthy controls (negative for both HCV and HBV antibodies) were enrolled in this study. HCV and EBV were assessed using both molecular (RT-PCR) and serological (enzyme-linked immunosorbent assay). Results: EBV was significantly undetectable in non-responders compared responders (96.2% vs. 77.0%, respectively, p<0.05). While there was a statistically significant higher percentage of EBV (>2000 copies/ml) among responders compared to non-responder patients (14.9% vs. 0%, respectively, p<0.05). Serologically, no statistically significant differences was found between both groups regarding EBV antibodies (p>0.05). However, a statistically significant higher percentage of past infection with EBV was detected among nonresponder compared to responders (100% vs. 81.8%, respectively) (p<0.05). Conclusions: The results of this study suggest that there is a unidirectional relation between EBV and HCV in our study subjects.