Most experimental and human data support the hypothesis that iron overload is a risk factor for cancer in general and liver cancer in particular. This oncogenic effect could be explained by an overproduction of reactive oxygen species and free radicals. In cirrhosis due to genetic haemochromatosis (homozygosity for the mutation C282Y in the HFE gene) there is an increase incidence of hepatocellular carcinoma. Few cases have been reported in genetic haemochromatosis with iron overload but without cirrhosis. In hepatocellular carcinoma developed in non cirrhotic liver there is a mild iron overload in more than 50% of cases. In these patients heterozygous and compound C282Y mutations are found in 36%. In black Africans, iron overload genetically determined but not linked to mutations in the HFE gene increases also the risk of hepatocellular carcinoma. Among the many factors (viral hepatitis, alcohol, tobacco etc.) which play a role in hepatic carcinogenesis, iron overload is probably an important one and therefore should be treated.