To determine the association between polycyclic aromatic hydrocarbon (PAH) exposure and risk of hepatocellular carcinoma, a case-control study nested within a community-based cohort was conducted in Taiwan. Baseline blood samples, collected from a total of 174 HCC cases and 776 matched controls, were used to determine the level of PAH-albumin adducts by competitive enzyme-linked immunosorbent assay. Conditional logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) to assess the effect of PAH-albumin adducts on risk of HCC. When compared to subjects in the lowest quantile, there was an increase in risk of HCC, with adjusted ORs (95% CI) of 1.0 (0.5-2.0), 1.2 (0.6-2.4) and 2.0 (1.0-4.2: P(trend)=0.08) for subjects in the 2nd, 3rd and 4th quantile, respectively. The corresponding adjusted ORs (95% CI) were 1.9 (0.6-6.1), 1.7 (0.6-4.9) and 2.1 (0.5-8.2; P(trend)=0.22), respectively, among subjects with high AFB(1)-albumin adducts; and 0.8 (0.3-2.7), 1.5 (0.6-3.5) and 2.9 (1.0-8.6; P(trend)=0.06), respectively, for those who were chronically infected with hepatitis B virus (HBV). The combination of PAH- and AFB(1)-albumin adducts above the mean and chronic HBV infection resulted in an OR of 8.2 (95% CI, 3.6-19.0; p<0.0001), compared to those with low adducts and no viral infection. These results demonstrate that PAH-albumin adducts are associated with an increased risk of HCC, especially among those with high aflatoxin exposure and chronic HBV infection. Environmental PAH exposure seems to enhance the hepatocarcinogenicity of chronic HBV infection.