Interleukin-8 (IL8) polymorphisms have been implicated in several cancers, but their roles in the pathogenesis of hepatocellular carcinoma (HCC) are largely unknown. The present study was designed to explore the association between IL8 polymorphism and the risk of HCC in a Chinese population. Four single nucleotide polymorphisms (SNPs) of the IL8 gene -251A/T, +781C/T, -353A/T and +678T/C were analyzed in 205 HCC patients and 208 healthy controls in a Chinese population. Serum levels of IL8 were detected in HCC patients and healthy controls. The association between IL8 polymorphisms and HCC risk was measured using the adjusted odds ratios (OR) and their 95% confidence intervals (CI) from multiple logistic regression analysis. Haplotype analysis and gene-environment interaction analysis was also performed. The serum level of IL8 was significantly higher in HCC patients compared with healthy controls (P < 0.001). After adjusting for confounding factors, no significant associations were found between -251A/T, +781C/T, -353A/T and +678T/C and HCC risk (all P > 0.05). Haplotype analysis showed that A(251)-C(781)-A(353)-C(678) conferred decreased risk of HCC onset (adjusted OR 0.31, 95% CI 0.13-0.77). No significant interaction effects were found between the four SNPs and HBV infection, cirrhosis, gender smoking and alcohol consumption (all P > 0.05). No association between -251A/T, +781C/T, -353A/T and +678T/C of the IL8 gene and the risk of HCC was found in this Chinese population, and the SNPs did not display any interaction with several environmental factors with regard to HCC risk. However, it appears that A(251)-C(781)-A(353)-C(678) is perhaps a protective haplotype for HCC.