Hepatocellular carcinoma, the most common primary cancer of the liver, results in significant morbidity and mortality. Several disease entities have been shown to predispose to hepatocellular carcinoma. In most cases, however, hepatitis B virus, hepatitis C virus, and cirrhosis are the principal etiologic factors. In HIV-positive patients, a significant increase in the incidence of certain malignancies has been noted. Although HIV and the hepatitis viruses share common modes of transmission, an increase in the incidence of hepatocellular carcinoma in the patients with HIV has not been observed. This finding may be a function of premature death in patients with HIV before the advent of effective antiretroviral therapy. The introduction of such therapy may alter the epidemiology of hepatocellular carcinoma and strain health services, because current treatment options targeting both the underlying causative viruses and liver cancer itself are unsatisfactory and are the subject of ongoing research.