The objectives of the study were to estimate the prevalence of anti-hepatitis C virus (HCV) positivity among blood donors from Chengdu, China, and to determine risk factors associated with infection. In this study, data were collected from volunteer blood donors between July 2006 and June 2007. Anti-HCV test was performed in 119,518 donors. To identify risk factors associated with HCV infections a case-control study was conducted in 305 unique HCV-seropositive blood donors and 610 seronegative donors matched for age and sex. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. The population attributable risk (PAR) to risk factor was estimated according to the Bruzzi's formula. The prevalence of anti-HCV positivity was 0.53% (95% CI: 0.489-0.572%). The final multivariate model included the following independent HCV risk factors: razor sharing (OR=29.16; 95% CI: 12.89-66.00), blood transfusion (OR=20.84; 95% CI: 3.76-115.45), acupuncture (OR=8.01; 95% CI: 3.16-20.30), a history of hospitalization, injections >10 years earlier, a family history of hepatitis B, dental treatment, and ear piercing. The PAR of risk factors are 68.4%, 6.3%, 14.1%, 23.1%, 29.5%, 29.3%, 38.9%, and 27.8%, respectively, and the total PAR is 98.3%. Infection with HCV among blood donors in Chengdu is associated with iatrogenic risk factors and beauty treatment-related risk. Razor sharing is an important risk factor for HCV infection. These results indicate that infection control measures in healthcare settings may reduce the burden of HCV infection and there is a need for development of effective educational programs to improve HCV knowledge among beauty culture professionals, barber cosmetologists, and the general public to avoid risk behaviors.