Recently, human leukocyte antigen (HLA) class-II gene polymorphisms have been reported to be related to Hepatitis C virus (HCV) infection and chronicity. The objective of this study was to explore the relationship of HLA-DP rs9277535 and HLA-DQ rs7453920 with the outcomes of HCV infection.The rs9277535 and rs7453920 were genotyped in 370 subjects with chronic HCV infection, 194 subjects with spontaneous HCV clearance, and 973 subjects with non-HCV infection from the Chinese population using the ABI TaqMan allelic discrimination assay.Logistic regression analyses showed that the minor allele A of rs7453920 significantly increased the susceptibility of HCV infection in dominant model (adjusted OR = 1.33, 95% CI: 1.04-1.71, P = 0.026) and additive models (adjusted OR = 1.30, 95% CI: 1.06-1.60, P = 0.012). Rs9277535 A allele significantly increased the risk of chronic HCV infection in dominant model (adjusted OR = 1.52, 95% CI: 1.01-2.28, P = 0.046). Haplotype AA showed a higher risk of HCV infection than the most frequent haplotype GG (adjusted OR = 1.37, 95% CI: 1.05-1.78, P = 0.018).The HLA-DQ rs7453920 and -DP rs9277535 mutations were significantly associated with HCV infection susceptibility and chronicity, respectively.