Objective:To investigate the association between the potentially functional polymorphisms in IL-12A and IL-12B and risk of cervical cancer. Methods:The case-control study was conducted in Jiangsu female population, including 404 cervical cancer cases and 404 cancer-free controls frequency-matched by age and residential areas. The genotype of the IL-12A rs568408, rs2243115 and IL-12B rs3212227 polymorphisms were determined by polymerase chain reaction restriction and fragment length polymorphism (PCR-RFLP) assays. Results:The IL-12A rs568408 GA/AA and IL-12B rs3212227 AC/CC variant genotypes were associated with a significantly increased risk of cervical cancer [adjusted odds ratio (OR)=1.43,95% confidence interval(CI)=1.06~1.93 and adjusted OR=1.30,95% CI=0.97~1.75, respectively], compared with their corresponding wild-type homozygotes. Moreover, a significant gene-gene interaction of these two loci were evident in the risk of cervical cancer (P for multiplicative interaction=0.048); subjects carrying variant genotypes of both loci had a 1.82-fold (95% CI=1.28~2.57) increased risk of cervical cancer. In the stratified analyses,the combined genetic effect was more pronounced in patients with early-stage tumors and those with more parities. Subjects carrying rs568408 AG/AA and rs3212227 AC/CC genotypes and having more than 2 parities showed a 6.00-fold (95% CI=2.86~12.56) elevated cervical cancer risk (P for multiplicative interaction=0.046). Conclusion:These findings indicate that IL-12A rs568408 and IL-12B rs3212227 may individually and jointly contribute to the risk of cervical cancer, and may modify cervical cancer risk associated with parity.