The factors leading to clearance or persistent infection of hepatitis C virus (HCV) were not well defined, and the importance of the host immune response has been highlighted. Therefore, the impact of the serum concentration and genetic polymorphism of several cytokines on the outcome of HCV infection warrant additional study. Enzyme-linked immunosorbent assay was employed to measure serum tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, and IL-10 concentrations on 72 hepatitis C patients and 180 controls. Furthermore, the association between single nucleotide polymorphism (SNP) of genes of these cytokines and hepatitis C infection was evaluated by polymerase chain reaction- restriction fragment length polymorphism and statistical analysis. These analyzed SNPs of cytokines included TNF-alpha G238A, TNF-alpha G308A, IL-4 C589T, IL-10 A1082G, IL-10 T819C, and IL-10 A592C. Serum levels of TNF-mu alpha, IL-4, and IL-10 were significantly higher in hepatitis C patients than that of controls (P < 0.001). Furthermore, the distribution of TNF-alpha G308A genotypes and alleles, but not others, was statistically different between patients and controls (P < 0.05). These data suggested the distribution of polymorphism at TNF-alpha G308A may be different between normal subjects and patients with chronic infection of hepatitis C.