〔Abstract〕 Objective To investigate the association between c.1311 C>T and c.1004 C>A of glucose-6-phosphate dehydrogenase(G6 PD) gene single nucleotide polymorphism(SNP) with the risk of G6 PD deficiency in Guangxi population. Methods 417 patients with G6 PD deficiency were randomly selected as case group, and 295 healthy patients were selected as control group. The c.1311 C>T and c.1004 C>A were genotyped using the SNPscanTM multiple SNP method, and the haplotype frequency of two sites were analyzed by SHEsis. Results In the case and control group, there were statistically significant differences in the distribution frequency of genotype TT, CC+CT and allele T at c.1311 C>T locus [TT vs CC:(P=0.001,OR=0.373, 95%CI=0.204-0.683); TTvsCC+CT:(P=0.001,OR=0.371, 95%CI=0.203-0.678); TvsC:(P=0.002,OR=0.601, 95%CI=0.435-0.829)];however, there was no significant difference in genotype and allele distribution frequency at c.1004 C>A locus(P>0.05). The results of the rate method showed that compared with genotype CC,the genotype CT at c.1311 C>T increased the expression level of G6 PD enzyme, while the genotype TT decreased the expression level of G6 PD enzyme(P<0.05), the haplotype analysis showed that C-C and T-C were associated with G6 PD risk(P<0.05). Conclusion In Guangxi population, c.1311 C>T locus genotypes TT, CC+CT and allele T were related to the decreased risk of G6 PD deficiency.