Objective:To investigate the association between potentially functional polymorphisms in IL12A and IL12B and risk of primary hepatocellular carcinoma (PHC). Methods:We genotyped three IL12A polymorphisms rs568408 (3’UTR G>A),rs2243115(5’UTR T>G) and IL12B rs3212227 (3’UTR A>C) using the RFLP-and PIRA-PCR assays in a case-control study of 538 HCC cases and 535 cancer-free controls. Results:The IL12A rs568408 GA/AA variant genotypes were associated with a significantly increasing risk of PHC[adjusted odds ratio (OR)=1.35,95% confidence interval (CI)=1.03~1.79],compared with their corresponding wild-type homozygotes. In the stratified analysis,rs568408 genetic effect was more pronounced in male and drinker (adjusted OR=1.46,95% CI=1.08~1.98 for male;adjusted OR=1.53,95% CI=1.07~2.18 for drinker). Conclusion:Our findings indicate that IL12A rs568408 may contribute to the risk of PHC.