Aurora A is considered a potential cancer susceptibility gene owing to overexpression or amplification of Aurora A gene that causes centrosome dysfunction, chromosome instability, tumourigenic transformation and checkpoint abnormalities. Functional coding region polymorphism F31I in the Aurora A gene has recently been shown to be associated with several human cancers, but its association with hepatocellular carcinoma (HCC) has yet to be investigated. Genetic polymorphism of Aurora A was investigated in 128 confirmed subjects with HCC and 128 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay. Allele and genotype associations of Aurora A F31I polymorphism with HCC susceptibility were observed in comparisons between the patient and control samples (respectively; P = 0.005, P = 0.012). The proportion of the genotypes containing I31 allele in patients with HCC (39.8%) was significantly higher than that in patients without HCC (22.7%) (P = 0.003). The distribution F31I genotype was significantly associated with increased risk of HCC (P = 0.003, odds ratio = 2.26, 95% confidence interval = 1.31-3.90 for FI + II genotypes vs FF genotype). Our results suggest for the first time that the Aurora A F31I polymorphism may be a genetic susceptibility factor for HCC.