Numerous studies have shown the presence of a highly significant excess of HBsAg, core and surface antibody in patients with hepatocellular carcinoma (HCC). An important factor in the aetiological association between hepatitis B and HCC may lie in the early age of infection. Although hepatitis B virus (HBV) DNA has been found in HCC tissue, there is no simple correlation between serum markers of hepatitis B infection and viral DNA in the tumour. Nevertheless, it is clear that in the case of HBV-associated HCC, integrated HBV sequences may be present in more than 80% of the tumours. The possible molecular basis for the resulting neoplastic transformation is discussed. Whatever the molecular basis of HBV involvement in the causation of HCC, immunization against HBV is likely to prevent primary liver cancer.