This study aims to comprehensively evaluate socio-demographic risk factors affecting the prevalence of HCV infection in the Khorezm region of Uzbekistan. Two hundred and twenty one patients with chronic hepatitis C (CHC) whose diagnosis was confirmed through HCV RNA detection were examined. Information was analyzed from patients’ official medical documents and a questionnaire was conducted. Clinical-epidemiologic, laboratory, instrumental, and statistical methods were employed. Factors such as male gender, low level of education, unemployment, dissociation between education and current activity, and history of criminal record were found to be determinants closely related to the prevalence of HCV infection, significantly increasing the risk of infection and development of CHC. The focus should be on populations confronting these risk factors. Preventive programs implemented with consideration of these risk factors will help reduce the intensity of the epidemic process and the frequency of HCV infection chronization.