Aim: There is a limited number of studies on the general population about prevalence of Hepatitis C virus (HCV) in Turkey. The estimated prevalence of HCV in the Southeastern region of the country was obtained from the data of the blood donors. There is no study reflecting the general population of this region, leading us to plan this study. Material and method: Four provinces in the Southeastern Anatolia were randomly selected and sample sizes were determined by Epi Info Programme, and blood samples were collected from 2888 individuals. Questionnaires in which demographic information and probable risk factors for Hepatitis C were investigated and were applied on subjects who gave their consent to participate in the study. Anti-HCV was examined by using Cobas Core II immunochemistry system (Roche). All positive samples were further tested for the presence of HCV RNA by RT-PCR. Crude odds ratios (OR) and 95% confidence intervals (CI) were calculated and Chi-square analyses were performed. Epi Info 2000 Programme was used to perform the analysis. Results: Of the 2888 individuals, 17 (0.6%) were anti-HCV positive and 13 (82%) of them were confirmed as positive for HCV-RNA. No difference was found between rural and urban regions with respect to HCV prevalence ( [Formula: see text] ). The prevalence of HCV in 35-44 years of age group was found to be different from those of the other age groups ( [Formula: see text] ). It was determined that the risk for HCV in this age group was 4.23 times ( [Formula: see text]; [Formula: see text];1.02-20.15; CI 95%:) higher with a prevalence rate of 1.6%. In this age group, anti-HCV was positive in 6 male (2.4%) and 2 female (0.8%), of whom 7 were living in urban (2.2%) and 1 in rural area (0.5%). The overall prevalence of HCV was not found to be different for sex ( [Formula: see text] ). Similarly, there was no difference between the married and single individuals for the prevalence ( [Formula: see text] ). Anti-HCV positivity did not change for the level of education. We could not determine any factor that might play a role in transmission of HCV. Conclusion: This is the first population-based study to be performed in order to determine the prevalence of HCV in the south-eastern region of Anatolia (Turkey). This region has a low prevalence of HCV. The extremely rare prevalence of homosexuality and intravenous drug addiction might have a role in this low prevalence.