HCC is a major problem in certain regions of the world, and an increasing problem in the United States. Although the precise mechanisms are not delineated, chronic viral hepatitis B and C clearly cause HCC. Epidemiologic evidence provides strong associations with both viral infections. The predominant pathway to HCC is through cirrhosis, but direct viral carcinogenic effects may also contribute, particularly for hepatitis B. Understanding of this epidemiology and pathophysiology provides the basis for the clinical evaluation, diagnosis, screening, and treatment of HCC.