The possibility to detect the antibody to hepatitis C virus (HCV) has allowed to estimate the prevalence of this virus in patients with hepatic disease, mostly in those with hepatitis considered non-A non-B. Literature shows that HCV causes about 75% of cases of cryptogenic hepatitis and more than the 90% of post-transfusional hepatitis. Circumstantial evidence suggests the existence of a relationship between parenterally-transmitted non-A non-B hepatitis (PTH) and primary liver cancer (PLC). With the advent of anti-HCV, it is now possible to assess directly whether or not there is a relationship between PTH and PLC. So anti-HCV was looked for in the sera of 365 patients with cirrhosis prospectively followed-up for early detection the development of PLC, using an enzymatic immunoassay (ELISA Ortho DS). At baseline anti-HCV was detected in 221 patients (60%). During 5-39 month 53 patients developed PLC and anti-HCV was detected in 68% of them. The univariate analysis demonstrated that alcohol abuse, anti-HBs and anti-HBc were the only covariates that were significantly associated with an increase risk of developing PLC. When these factors were introduced in the step wise regression analysis, age and alcohol were found to be the only independent risk factors. The high prevalence of anti-HCV found in patients with cirrhosis and PLC suggests that HCV might play a role in this tumor; the frequent co-occurrence of HCV and HBV markers suggests that HCV-HBV coinfection might be pathogenically important; alcohol was the most important non-viral risk factor for PLC.