Previous studies have suggested that the human leukocyte antigen (HLA) is involved in the etiology of Crohn's disease (CD); however, few reports are available on the association between HLA class I antigens and CD in Japan. In this study, we performed association analysis of HLA class I antigens in CD using 208 Japanese patients and 384 healthy controls. We identified novel positive associations between CD and HLA-A*02:01 (odds ratio (OR) = 1.64, P = 0.016) and HLA-A*02:07 (OR = 2.31, P = 0.0067) and confirmed previously reported positive associations between CD and HLA-Cw*14:02 (OR = 2.18, P = 0.0021) and HLA-B*51:01 (OR =1.70, P = 0.033). We also identified novel negative associations between CD and HLA-A*24:02 (OR = 0.60, P = 0.0047) and HLA-B*07:02 (OR = 0.38, P = 0.0041). Although the associations were not significant after full Bonferroni correction, we suggested that HLA class I genes have dual functions, susceptibility and resistance in controlling the development of CD.