Interleukin-32 (IL-32), a pro-inflammatory chemokine, has been reported to be involved in inflammatory, infectious diseases and even cancers. This study aimed to investigate whether two genetic variants (rs28372698 and rs12934561) of IL-32 were associated with susceptibility to endometrial cancer (EC) in Chinese Han women by a hospital-based study with 272 EC patients and 337 healthy controls. Our results showed that the frequencies of TT genotype (P = 0.012, OR = 2.37, 95 % CI = 1.32-4.28) and T allele (P = 0.026, OR = 1.320, 95 % CI = 1.036-1.681) of rs28372698 in EC patients were significantly higher than controls. Clinical analyses indicated the TT genotype frequency was relevant to high clinical stage and cervical invasion. Furthermore, the frequencies of CC genotype (P = 0.0077, OR = 1.62, 95 % CI = 1.05-2.50) and C allele (P = 0.043, OR = 1.269, 95 % CI = 1.011-1.592) of rs12934561 were also significantly higher in EC patients than controls. Stratification analyses revealed that CC genotype was more frequent in endometrioid adenocarcinoma or EC without parametrial invasion. This study demonstrates that IL-32 gene polymorphisms are significantly associated with increased EC susceptibility in Chinese Han women.