Aurora kinase A (AURKA) is a serine threonine kinase which affects chromosomal separation and mitotic spindle stability through interaction with the centrosome during mitosis. Two functional nonsynonymous polymorphisms of the AURKA gene (Ile31Phe and Val57Ile) have been reported recently. We analyzed the association between the two polymorphisms and risk of the occurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Guangxi population consisting of 348 patients with HCC and 359 control subjects, and then validated the significant association in the Guangdong population consisting of 440 cases and 456 controls. All of the participants were of Chinese origin and HBV carriers. The two polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay or Sequenom MassARRAY iPLEX platform. In the Guangxi population, carriers of the AURKA 31Phe allele (Ile/Phe + Phe/Phe) were significantly associated with decreased susceptibility to HBV-related HCC when compared with noncarriers (Ile/Ile) (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.46-0.86, P = 3.4 x 10(- 3)). On the contrary, no significant association was found between Val57Ile and HBV-related HCC occurrence. The association of Ile31Phe with HBV-related HCC occurrence was confirmed in the Guangdong population (OR = 0.64, 95% CI = 0.49-0.83, P = 8.0 x 10(-4)). The pooled analysis gave a joint P value of 5.5 x 10(-6) (joint OR = 0.63, 95% CI = 0.52-0.77). Our findings suggest that AURKA Ile31Phe may play a role in mediating the susceptibility to HBV- related HCC among Chinese.