Abstract Background: Egypt has the highest known prevalence of HCV in the world, a problem which represents a major chal-lenge to healthcare policymakers in the country. Aim of Study: This study aimed to highlight on the prev-alence of HCV infection in rural areas of this country and to clarify the association between different risk factors and the prevalence of HCV infection. Material and Methods: A screening campaign was con-ducted in five villages present in rural Menoufia Governorate. Blood samples from consented participants were tested for HCV antibodies. For assessment of the contribution of different risk factors with hepatitis C infection, we interviewed partic-ipants to complete the study questionnaire. Results were tabulated and analyzed by suitable statistical tests to assess the prevalence of HCV infection in these areas and possible risk factors that are significantly associated with infection. Results: Out of 14000 participants, 14.8% (n=2071) of the screened sample tested positive for HCV antibodies. Various risk factors were significantly associated with higher risk for acquiring HCV including parenteral anti-schistosomaiasis therapy, invasive medical procedures and other important risk factors. Conclusion: One of each six in the population of rural Menoufia is seropositive for HCV. Our results thus confirm the severity of the current disease burden in the Nile Delta of Egypt. There are significant risk factors associated with HCV infection, suggesting the need for more strict infection control measures specially upon using invasive medical procedures.