Objective To explore the potential association between HLA-DRB1 Alleles and systemic scleroderma (SSc) of the Zhuang Nationality in Guangxi region. Methods Polymerase chain reaction-special sequence primers (PCR-SSP) was used to study the HLA-DRB1 alleles in 58 patients with SSc and 50 healthy controls of the Zhuang Nationalty in Guangxi Province. Comparisons between groups were performed with χ2 test or exact probabilities. Results Sixteen HLA-DRB1 alleles were discovered from the specimens,including 14 in the SSc specimens, and 16 in the control specimens. Among them,the allele frequencies of HLA-DRB1 * 1301 (7.760%, OR=9.000, χ2=4.341, P=0.037), HLA-DRB1 * 1305 (11.207%, OR=3.322,χ2=4.206, P=0.040) and DRB1 * 15 (26.724%, OR=2.679, χ2=6.038, P=0.014) were significantly higher in SSc patients than those of the controls (respectively for 1.000%, 4.000%, 15.000%). Conclusion Our data suggest that the HLA-DRB1 * 1301, HLA-DRB1 * 1305 and HLA-DRB1 * 15 may be the susceptible genes of SSc in Zhuang nationality population.