BACKGROUND Syphilis is a sexually transmitted infection (STI) caused by the Treponema pallidum subspecies pallidum spirochete bacterium. The association of human leukocyte antigen (HLA) with syphilis has been reported in several populations, but not in the Chinese population. Furthermore, serology methods have mostly been used in previous studies investigating the association between STIs and HLA alleles. The objective of this study was to analyze the association of the HLA-DRB1 alleles and susceptibility to syphilis in the Chinese population. METHODS A polymerase chain reaction with sequence-specific primers (PCR-SSP) method was used to genotype HLA-DRB1 alleles in 196 syphilis patients and 500 healthy controls. RESULTS The HLA-DRB1*14 allele was more prevalent in syphilis patients than in the healthy controls (p=0.013; corrected p<0.05). CONCLUSIONS The allele HLA-DRB1*14 was found to be associated with susceptibility to syphilis in the Chinese population.