Abstract: Objective To investigate the interaction between polymorphism in TOX3 gene and environment factors in sporadic breast cancer.Methods The TaqMan single nucleotide polymorphism(SNP)assay was carried out to detect the dimorphism at the rs3803662 and rs9302556 SNP loci.The risk of sporadic breast cancer with 95%CI was estimated by unconditional logistic regression.The interaction of gene-gene,gene-environment and interaction coefficient was evaluated by unconditional logistic regression.The best interaction model was built by MDR.Results The strong positive interaction was observed between variant genotype of rs3803662 and rs9302556,and between variant genotype of TOX3 and environment factors,such as rs3803662,benign breast disease,oral contraceptives≥1 year and so on.There were a significant dose-response relationship of interaction effects between variant genotype of TOX3 and menstruation years and BMI(P＜0.05).The variant genotypes of rs3803662,rs9302556,benign breast disease,oral contraceptives and other 7 factors were contained in the best interaction model.Conclusion The interaction effects between variant genotype of rs3803662 and rs9302556 loci in TOX3 gene and environment factors play an important role in increased risk of breast cancer.