To investigate the role of HLA-DQA1 genotypes and their interaction with HLA-DRB1 in the pathogenesis of rheumatoid arthritis (RA) in Taiwan, HLA-DQA1 was determined in 71 patients with RA and 108 healthy controls by SSP-PCR method. HLA-DRB1 and HLA-DQA1 were simultaneously detected in 55 RA patients and 101 healthy controls. PCR/SSOP method was used to determine the HLA-DRB1 genotypes, and the subtypes of HLA-DR4 were determined by cloning and sequencing. The phenotypic frequency of HLA-DQA1*0301 was significantly lower in RA than in controls, and, in contrast, the HLA-DQA1*0302 and DQA1*0303 were significantly higher in RA than in controls. The associations of DQA1*0301, *0302, and *0303 with RA were independent of DR4 and DRB1*0405. Moreover, the interactions between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303 could enhance the development of RA. We also found that the prevalence of bone erosion and seropositivity of rheumatoid factor (RF) were significantly higher in HLA-DQA1*0303 positive RA patients than in healthy controls. HLA-DQA1*0302 and DQA1*0303 are the risk factors for susceptibility to RA, while HLA-DQA1*0301 is a protective factor. A synergistic effect for the susceptibility to RA can be found between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303. We also found that the HLA-DQA1*0303 was related to bone erosion and seropositivity of RF in RA patients.