Objective To investigate loci polymorphisms of TNF gene rs1800629 and rs361525 and the association of gene ⁃ environment interaction with the susceptibility to unexpected recurrent spontaneous abortion （URSA）. Methods Genotyping of TNF gene（rs1800629 and rs361525）was performed on the samples from 150 URSA patients and 150 healthy volunteers using SNaPshot method. Correlation analysis and generalized multifactor dimensionality reduction（GMDR）were used to analyze the relationship between URSA and polymorphisms of two loci. Results Multiple regression analysis showed that no significant difference in genotype of the TNF gene rs1800629 and rs361525 was observed between the case group and the control group（P < 0.05）. However，after stratified analysis，we found that in the dominant inheritance mode of rs361525 locus，the risk of RSA in A allele carriers significantly was increased in twice（OR = 2.402，95% CI：1.041 ~ 5.545）. GMDR analysis showed a significant gene⁃environment interaction among rs1800629，rs361525 and job′s character. Conclusion The TNF gene A allele of rs361525 is associated with URSA（n = 2）susceptibility and the TNF gene⁃environment interac⁃ tion may increase the risk of USRA. No association between rs1800629 and USRA is found.