Objective:To explore the relationship of NSCL/P with MTHFR gene polymorphism in Xinjiang Uyghur and Han popula-tion and the ethnic difference.Methods:rs1801131 and rs1801133 polymorphism was detected by SNaPshot genotype method in 170 children with NSCL/P and 100 healthy controls of Uyghur and Han population.Results:Rs1801133 TT and T allele was statistically difference between 2 nationalities(P <0.05),Rs1801133 CT and CT +TT genotypes in total case group and control group were sta-tistically different(P <0.05);Rs1801131 and rs1801133 conjoint analysis showed that between the 2 nationalities and between case and control groups of total population were statistically different(P <0.05);rs1801131 genotype between 2 nationalities or total cases and controls were not statistically different(P >0.05).Conclusion:Rs1801133 TT and T allele in Han nationality are more likely to suffer from NSCL/P than in Uyghur,rs1801133 CT and CT +TT genotypes are protective factors.Rs1801131AC and rs1801133CC conjoint is relevant to NSCL/P,and the risk in Uyghur is higher than in Han.MTHFR rs1801131 gene polymorphism may not be relat-ed with NSCL/P in Uyghur or Han.