High prevalence of hepatitis c virus (HCV) infection in some areas necessitates more investigations of the causative factors. Genetic factors that cause disruption in operation or secretion of interleukin 10 (IL-10), an anti-inflammatory cytokine, may play a role in the intensity of the disease. The aim of this study was to evaluate genetic variants of IL-10 gene polymorphisms in HCV patients and their relationship with HCV disease. Fifty HCV patients and the same number of healthy individuals who were referred to hepatitis clinic in Mashhad, northeast of Iran, were recruited. Genomic DNA was extracted from whole blood. Genotyping for IL-10 gene promoter polymorphisms in three positions (-1082 G>A, -819 C>T and -592 C>A) was conducted by amplification refractory mutation system-polymerase chain reaction. Haplotype analysis was performed using PHASE software. In a recessive analysis model of the -1082 position (GG vs. AA+AG), GG genotype was more common in patients (adjusted p=0.02; OR=4.66 [95% CI 1.31-16.35]). Also, ATA haplotype was more prevalent in HCV patients (adjusted p=0.061; OR=1.87 [95% CI 0.97-3.61]). Also, ATC/GCA diplotypes were more common in controls (adjusted p=0.002; adjusted OR=0.27 [95% CI 0.11-0.63]). Although we found a possible association between IL-10 promoter polymorphisms and HCV infection, certain genotypes or diplotypes may confer a higher risk or susceptibility for developing HCV infection.