Objective To explore the distribution characteristics of S100B gene rs1051169 G/C and rs9984765 T/C polymorphisms in Guangxi population, and to compare the distribution differences among different races and districts population. Methods Polymerase chain reaction-single base extension (SBE-PCR) and DNA sequencing were used to detect the genotype of rs1051169 G/C and rs9984765 T/C among 398 individuals in Guangxi. The results were compared with the allele and genotype of other four populations (HapMap-CEU, HapMap-YRI, HapMap-JPT, HapMap-HCB) from Haplotype Map(Hap Map). Results There were GG, CG and CC genotypes at the rs1051169 G/C of S100B gene in Guangxi population, with frequencies of 41.2%, 44.7% and 14.1%, respectively, and G and C allele frequencies were 63.6% and 36.4%, respectively. TT, CT and CC genotypes were found at rs9984765 T/C, with frequencies of 47.7%, 44.5% and 7.8%,respectively, and allele frequencies of T and C were 70.0% and 30.0%,respectively. There were no significant differences in genotype and allele frequencies of rs1051169 G/C and rs9984765 T/C among male and female in Guangxi population (P>0.05). The genotype and allele frequency of rs1051169 G/C in Guangxi population showed significant difference as compared with HapMap-CEU, HapMap-YRI and HapMap-JPT (P<0.01), the allele frequency of rs1051169 G/C in Guangxi population showed significant difference as compared with HapMap-HBC (P<0.05), but their genotype frequencies showed no significant difference as compared with HapMap-CEU (P>0.05). The genotype and allele frequency of rs9984765 T/C in Guan gxi population showed significant difference as compared with HapMap-YRI, HapMap-JPT and HapMap-HBC (P<0.05), there was no significant difference compared with HapMap-CEU (P>0.05).Conclusion The polymorphisms of rs1051169 G/C and rs9984765 T/C in S100B gene in Guangxi populations, and their polymorphisms are different from different races and district populations.