【Abstract】Objective To analyze the correlation between rs1801131 polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and the susceptibility to unexplained recurrent spontaneous abortion (URSA).Methods 100 patients with unexplained recurrent spontaneous abortion admitted to our hospital from August 2017 to March 2019 were selected as the study group, and 100 healthy women in outpatient physical examination at the same time were selected as the control group. The general data and blood samples of all subjects were collected, the rs1801131 polymorphism of MTHFR gene was detected by DNA PCR sequencing. The serum homocysteine (Hcy) level was measured by Hitachi 7020 automatic analyzer. The he serum folate (FA) level was detected by enzyme-linked immunosorbent assay (ELISA). Logistic regression was used to analyze the relationship between rs1801131 polymorphism of MTHFR gene and the susceptibility of recurrent spontaneous abortion. Results There was no significant difference in age, menstrual cycle, BMI, blood glucose, TG, FA and Hcy level between the study group and the control group (P＞0.05). The genotype and allele frequency of rs1801131 of MTHFR gene in the study group and the control group were consistent with Hardy Weinberg equilibrium. Compared with the control group, the frequencies of A allele and wild type AA genotype at rs1801131 of MTHFR gene in the study group were significantly reduced. The frequencies of C allele, heterozygous and homozygous mutation AC + CC genotype increased significantly (χ2=4.603, 4.542, P=0.032, 0.033). Compared with the AA genotype at rs1801131 of MTHFR gene, the FA level of AC+CC genotype decreased and Hcy level increased (t=14.068, 32.216, P＜001). Carrying AC+CC genotype, high Hcy level and low FA level could increase URSA susceptibility (OR=1.437, 95% CI: 1.234～1.673, P=0.012; OR=1.257, 95% CI: 1.112～1.421, P=0.035; OR=1.175, 95% CI: 1.620～2.920, P＜0.001). Conclusion MTHFR rs1801131 allele C and genotype AC+CC may increase the susceptibility of URSA, which may be related to the decrease of FA level and the increase of Hcy level.