To evaluate the association between Foxp3 gene polymorphisms (rs3761548 and rs5902434) and susceptibility to endometrial cancer (EC), we report a hospital case–control study involving 602 women, consisting of 269 patients with EC and 333 healthy controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Our results suggest that the frequency of the A allele in rs3761548 in patients with EC was significantly lower than that in healthy controls (20.3% vs 26.4%, odds ratio [OR] 0.71, 95% confidence interval [CI]: 0.54–0.93, P = .012), while the heterozygous AC genotype showed a significant protective effect on EC in codominant, dominant, and overdominant models (adjusted OR 0.64, 95% CI: 0.45–0.91, P = .039; OR 0.65, 95% CI: 0.47–0.91, P = .011; OR 0.67, 95% CI: 0.47–0.94, P = .02, respectively), and AA genotype was more frequent in patients with cervical invasion (recessive model: OR 3.55, 95% CI: 1.10–11.44, P = .046). Moreover, ATT/ATT genotype (rs5902434) was conferred a lower risk of EC in the recessive model (adjusted OR 0.58, 95% CI: 0.35–0.96, P = .031). From the data generated, we conclude that Foxp3 promoter polymorphisms are associated with susceptibility to EC in Chinese Han women.