In this study, we aimed to explore the associations between HLA-A\B\DRB1 polymorphisms and the risks of vulvar lichen sclerosus (VLS) or squamous cell hyperplasia of the vulva (SCHV) in Han Chinese women. We enrolled 76 Han Chinese women with VLS (Group A), 74 with SCHV (Group B), and 66 healthy women (control group) in this study. Polymerase chain reaction amplification with sequence specific primers (PCR-SSP) was used to determine HLA-A\B\DRB1 polymorphisms. Compared with the control group, HLA-A*11, -B*15, and -DRB1*12 were present at a higher frequency in groups A and B, while HLA-B*13 was present at a higher frequency in group A. Fewer women in group A carried HLA-A*31, -DRB1*01, and -DRB1*03 genotypes and fewer women in group B carried HLA-B*40 and -DRB1*03 genotypes. Significant differences were found between group B and the control group for HLA-A*11, -B*15, -B*40, and -DRB1*03, and between group A and the control group for HLA-B*15 and -DRB1*12. The HLA-A*11, HLA-B*13, HLA-B*15, and HLA-DRB1*12 genotypes were associated with a higher risk of VLS, while the HLA-A*31, HLA-DRB1*01, and HLA-DRB1*03 genotypes were associated with a lower risk of VLS. In addition, carrying HLA-A*11, HLA-B*15, HLA-B*35, and HLA-DRB1*12 genotypes, and carrying HLA-B*40 and HLA-DRB1*03 genotypes were found to be risk or protective factors for SCHV, respectively.