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Background: The genetic basis of susceptibility to hepatocellular carcinoma (HCC) is poorly understood. Genomic DNA was available from 98 patients with HCC, 77 familial controls, 97 controls from Hong Kong and 96 Northern European controls (NECs)., Methods: Polymorphisms of interleukin (IL)-1beta; IL-1 receptor antagonist (IL-1RN); IL-10 promoter (positions -1082, -819, and -592); and tumor necrosis factor (TNF)-alpha promoter (TNF-a -238 and -308) were investigated., Results: There was marked restriction in the distribution of the IL-1beta and IL-1RN genotypes among Chinese subjects with a predominance of the IL-1beta*1,1 and IL-1RN*1,1 (for unrelated controls compared with NECs only for IL-1beta: chi2 = 15.32, Pc = 0.000091 and for IL-1RN: chi2 = 16.08, Pc = 0.000061). For IL-10, the distribution of alleles was reversed in Chinese vs NECs. The TNFA*2 allele (TNFA -308 A), which is associated with high TNF-alpha production both in vivo and in vitro, was found in <10% of Chinese but was present in 33% of NECs (chi2 = 21.52, Pc <0.0000035)., Conclusion: Though this study failed to highlight specific associations between any of the polymorphisms tested and the HCC in Hong Kong Chinese, the differences in the distribution of tested alleles may, in part, account for the increased susceptibility of the Chinese population to develop HCC.