Vitamin D has been considered as an immune modulator, and exerted the effect through the vitamin D receptor (VDR). This study investigated the associations of single-nucleotide polymorphisms (SNPs) of VDR with the outcomes of Hepatitis C virus (HCV) infection. Three SNPs (rs2228570, rs757343 and rs739837) were genotyped by TaqMan assay among Chinese population, including 538 HCV spontaneous clearance subjects, 834 persistent infection subjects and 1030 uninfected subjects. Binary logistic analyses were used to control the effects of confounding factors. The results showed that subjects with the rs757343 A allele and rs739837 A allele had the significantly reduced risk of HCV susceptibility (all PBonferroni<0.05 in dominant/additive model). In the stratified analysis, the protection of rs757343 A allele and rs739837 A allele against HCV infection remained effective in some subgroups. In addition, patients carrying rs739837 CA genotype were less prone to develop persistent infection (PBonferroni=0.033) and such effect still work in several subgroups in the stratified analysis. Furthermore, haplotype analysis indicated that when compared with the most frequent GC haplotype, the haplotype carrying AA (odds ratio (OR)=0.66, 95% confidence interval (CI)=0.56-0.78) and GA (OR=0.64, 95% CI=0.47-0.85) suggested a protective effect. Our findings indicated that the polymorphisms of VDR are associated with the outcomes of HCV infection among Chinese population.