Relevant studies on the etiology and pathogenesis of hepatocellular carcinoma (HCC) have been reviewed. Chronic hepatitis B virus infection and food aflatoxin B1 contamination have been identified as the major and possibly synergistic risk factors for HCC in endemic areas. Chronic hepatitis C virus is also an important risk factor. Cirrhosis of any etiology, particularly viral and alcoholic, is an important step toward HCC. Many other factors, such as alcohol drinking, cigarette smoking, hormone and even vitamins may also contribute to the development of HCC. Tumor suppressor p53 gene mutation was demonstrated in 25-30% of the patients with HCC from endemic regions. Hepatocarcinogenesis is therefore a multifactorial and multistep process involving initiator-induced multiple genetic alterations and promoter-induced proliferation and progression. Preventive measures to reduce risk factors and adequate therapy to prevent cirrhosis development could be effective ways to reduce or eradicate HCC.