Epidemiological evidence indicates that HCV plays an important role in the pathogenesis of many cases of hepatocellular carcinoma (HCC) in both hemispheres. In southern European countries the proportion of HCCs attributable to HCV is high, whilst in the USA this fraction is definitely smaller. These differences cannot be explained merely on the basis of the different prevalences of HCV in the corresponding general populations. Thought the mechanisms of HCV-related carcinogenesis are still obscure, it is clear that HCV alone or in conjunction with other environmental risk factors such as alcohol consumption or HBV infection can contribute to the epidemiological and clinical heterogeneity of HCC. Preliminary data indicate that HCV-related tumors arise in older patients, have a less aggressive course, and are more often associated with cirrhosis than HBV-related tumors.