Background <p>Hepatitis C virus (HCV) poses a significant health risk to hemodialysis patients because of their increased susceptibility to infection, especially in resource-limited environments. HCV infection can result in severe complications such as liver failure and higher mortality rates. This study evaluated the prevalence of HCV infection among patients undergoing hemodialysis and identified critical risk factors to enhance targeted prevention strategies.</p> Methods <p>A cross-sectional, observational study was conducted at Damascus Hospital and Surgical Kidney Hospital between 2017 and 2022 to assess HCV prevalence and associated risk factors in hemodialysis patients. Data included demographics, dialysis duration, dialysis route, history of blood transfusion, liver function test results, and anti-HCV antibody results. Statistical analyses were performed using chi-square tests, ANOVA, and t-tests.</p> Results <p>Of the 200 hemodialysis patients, 24% tested positive for HCV virus. Infection rates were significantly higher in patients with longer dialysis durations (<i>p</i> = 0.001), double-lumen catheter use (32.5% of the sample), and history of blood transfusions (20% of the sample). Patients who primarily underwent AV fistula dialysis showed comparatively lower infection risk. Additionally, demographic factors such as urban residency and older age were observed in a higher proportion of HCV-positive patients, although the difference was not statistically significant.</p> Conclusion <p>This study highlighted a significant HCV burden among hemodialysis patients, with infection risk correlating with dialysis duration, blood transfusion history, and catheter type. These findings underscore the need for consistent infection control measures and targeted interventions to reduce HCV transmission and improve patient outcomes, especially in regions with limited healthcare resources.</p>