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Background and Aims Hepatitis C virus (HCV) commonly causes a chronic infection but portion of hemodialysis patients are able to resistant to HCV infection even clear the virus naturally. Interleukin-10 (IL-10) and interleukin-12 (IL-12) are crucial regulators of the immune response to T-helper 1 (Thl) or T-helper 2 (Th2) categories and play a role in autoimmune and infectious diseases. This study was undertaken to investigate the possible association of genetic polymorphisms of 3 untranslated region (3UTR) of the IL-12B (-1188) and IL-10 (-592 and -819) andhepatitis C in Chinese Han hemodialysis (HD) patients. Methods The genotyping of IL-12B 3UTR and IL-10 -592 and -819 were performed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. Results Compared with the IL-12B-AA genotype, CC and combined CC/AC genotypes were associated with a significant decreased risk of HCV infection in Chinese hemodialysis patients (P <0.001). However, the IL-10-592 and -819 genotypes were not found significant difference both between the anti-HCV (+) and anti-HCV (-) patients (P>0.05) and the persistent infection and viral clearance HD patients (P>0.05). Conclusions The present study indicated that the polymorphisms of IL-12B 3UTR might contribute to the susceptibility of HCV infection in Chinese HD population.