Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and has a marked difference in geographic distribution. More than 80% of HCC cases occur in developing countries, especially the Far East and Southeast Asia. Although immunization has been successful against hepatitis B virus (HBV), a changing disease burden of HCC has been observed in many parts of the world because of the increasing prevalence and duration of hepatitis C virus (HCV) infection in these countries. In addition, the age-specific incidence of HCC has progressively shifted toward younger people. Hepatitis B genotypes B and C are prevalent in the Far East and Southeast Asia, and the clinical relevance of HBV genotypes has become increasingly recognized. Compared with genotype C, genotype B is associated with earlier hepatitis B e antigen seroconversion, slower progression to cirrhosis and less frequent development of HCC. By using periodic examinations of serum alfa-fetoprotein levels and abdominal ultrasonography, small HCC can be detected and treated earlier. However, prevention of HBV and HCV infections as well as effective treatment of the chronic viral infections with timely interventions are still needed for the global control of HCC, particularly in the Far East and Southeast Asia.