Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) are not well-established vinyl chloride monomer (VCM)-induced diseases. Our aim was to appraise the role of VCM, alcohol intake, and viral hepatitis infection, and their interactions, in the etiology of HCC and LC. Thirteen cases of HCC and 40 cases of LC were separately compared with 139 referents without chronic liver diseases or cancer in a case-referent study nested in a cohort of 1,658 VCM workers. The odds ratios (ORs) and the 95% confidence intervals (CIs) were estimated by common methods and by fitting models of logistic regression. We used Rothman's synergy index (S) to evaluate interactions. By holding the confounding factors constant at logistic regression analysis, each extra increase of 1,000 ppm times years of VCM cumulative exposure was found to increase the risk of HCC by 71% (OR = 1.71; 95% CI, 1.28-2.44) and the risk of LC by 37% (OR = 1.37; 95% CI, 1.13-1.69). The joint effect of VCM exposure above 2,500 ppm times years and alcohol intake above 60 g/day resulted in ORs of 409 (95% CI, 19.6-8,553) for HCC and 752 (95% CI, 55.3-10,248) for LC; both S indexes suggested a synergistic effect. The joint effect of VCM exposure above 2,500 ppm times years and viral hepatitis infection was 210 (95% CI, 7.13-6,203) for HCC and 80.5 (95% CI, 3.67-1,763) for LC; both S indexes suggested an additive effect. In conclusion, according to our findings, VCM exposure appears to be an independent risk factor for HCC and LC interacting synergistically with alcohol consumption and additively with viral hepatitis infection.