Abstract: Background/Aim: Recent data have shown that the clinical outcome of hepatitis C virus (HCV) infection may be influenced by the host genetic factor. The aim of this study was to investigate whether particular human leukocytes antigen (HLA) molecules are associated with the susceptibility to HCV infection in the Korean population.Methods: One hundred and thirty‐seven patients with chronic HCV infection and 206 normal individuals were examined for HLA class I and II molecules.Results: In class I antigens, the frequencies of HLA‐A3 (relative risk (RR)=3.5, P<0.04), HLA‐B35 (RR=2.0, P<0.03), and HLA‐B46 (RR=2.5, P<0.02) significantly increased in chronic HCV carriers compared with the controls. The frequencies of DRB1*0803, DQB1*0601 and DQB1*0604 were significantly higher in chronic HCV carriers than in controls (RR=2.5, P<0.005; RR=1.8, P<0.05; RR=1.9, P<0.04, respectively). On the other hand, the frequencies of DRB1*0301, DQA1*0501 and DQB1*0201 were significantly lower in chronic HCV carriers than in normal controls (RR=0.2, P<0.03; RR=0.4, P<0.004; RR=0.5, P<0.02, respectively). The haplotype DRB1*0803−DQB1*0601 significantly increased (RR=2.5, P<0.02) while the DQA1*0501−DQB1*0201 significantly decreased (RR=0.2, P<0.03) in chronic HCV carriers compared with normal controls. In stratification analysis to investigate the interrelationships among the associated alleles, DRB1*0803 and DQB1*0601 were associated with HLA‐B46, particularly in patients with chronic HCV carriers.Conclusions: These results suggest that particular HLA alleles may have an influence on chronic HCV infection as a host genetic factor in the Korean population.