OBJECTIVE To investigate the relationship between the recurrent spontaneous abortion and soluble human leukocyte antigen (HLA) DQB1 gene polymorphism. METHODS Sixty one cases with recurrent spontaneous abortion were included in study group. Of them, 31 were anticardiolipin antibody (ACA) positive, while 30 were negative. Twenty eight cases were with early abortion, 22 were with late abortion, and 11 were with both early and late abortions. Thirty six women without abnormal pregnancy history were recruited as control group. HLA-DQB1 genotyping was carried out by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP). RESULTS The frequency of DQB1*0201allele in the study group (16.4%, 20/122) was higher than that in the control group (8.3%, 6/72), but the difference was not statistically significant (P > 0.05). The frequency of 57 site with non Asp in the study group was significantly higher than that in the control group (P < 0.05). The frequencies of both DQB1*0201 and *0303 were significantly different among early abortion, late abortion and both early and late abortion groups (P < 0.05 and P < 0.05). The frequency of DQB1*0201 was significantly higher in the early abortion group than that in the late abortion group (P < 0.01). The frequency of DQB1*0303 was significantly increased in the late abortion group when compared to that in the early group (P < 0.01). The frequency of DQB1*0303 was found to be significantly higher in patients with ACA positive than that in ACA negative group (P < 0.05). CONCLUSIONS The 57 site with non Asp may be a gene related to recurrent spontaneous abortions. DQB1*0201 may be correlated to the early abortion, while DQB1*0303 correlated to the late abortion and abortion with ACA positive.