Abstract： Objective To determine the allele and genotype frequencies of two single nucleotide polymor-phisms (SNPs) 677C/T,1298A/C in the methylenetetrahydrofolate reductase(MTHFR) gene in Chinese Southern Han individuals, and to assess whether there are differences in alleles frequencies among rheumatoid arthritis(RA) patients and normal controls. Methods 187 subjects(101 normal controls and 86 RA patients) were analyzed. The slide frequencies were carried out with polymerase chain reaction-restriction fragment langth polymorphism (PCR-RFLP). The two MTHFR SNPs Hardy-Weinberg equilibrium, linkage disequilibrium were analyzed with population genetics methods. Results The allele distribution of SNPs was in good unity with Hardy-Weinberg eqilibrium. The genotype frequencies of 677CC, CT, TT were 36.0%, 51.2%, 12.8%, respectively, in RA group, and 42.6%, 44.6% ,12.9%, respectively, in controls. The genotype frequencies of 1298AA,AC、CC were 60.5%、32.6%、 7.0%, respectively, in RA group, and 49.5% ,46.5% ,4.0% ,respectively, in controls. The frequencies of rarely allele 677T were 38. 4% and 35.1% in RA and controls. The 1298C were 23.3% and 27.2% in RA and controls. Allele frequencies were similar between RA group and controls, and there is no linkage between two SNPs and RA. The relationship between 677C/T and 1298A/C was strong linkage disequilibrium. Conclusions The research pro-vided Chinese southern Han population genetics data on MTHFR gene. The relationship between 677C/T and 1298A/C was strong linkage disequilibrium.