Several data indicate that iron may be involved in the pathogenesis of hepatocellular carcinoma (HCC). A high prevalence of HCC has been reported in patients with genetic hemochromatosis and the risk of HCC appears to be related to the amount and duration of iron overload. Iron, which has been demonstrated to facilitate persistent hepatitis B or C infection, could also act as a co-factor in the pathogenesis of HCC in patients with hepatitis B or C. Among the possible mechanisms by which iron could exert its cancerogenetic potential, free radicals production responsible for heritable genetic alterations appears to be one of the most important, although the fibrogenetic capability of iron, potentially leading to cirrhosis, cannot be underestimated.