Chronic hepatitis C infection (HCV) accounts for approximately 50% of the cases of hepatocellular carcinoma (HCC) in the United States. Cirrhosis or an advanced stage of fibrosis is the major risk factor of HCC; patients with cirrhosis are recommended to undergo surveillance with alpha-fetoprotein and ultrasound. Alpha interferon (IFN-alpha) is associated with a reduced risk of HCC in patients with chronic infection but insufficient data exist to recommend treatment of patients with cirrhosis and HCV for this reason alone. Resection and liver transplantation are the only "curative" therapies available. Advanced fibrosis or cirrhosis in patients with HCC limits the number of patients for whom resection is applicable. Moreover, the remaining liver is at high risk of developing a second primary tumor. Partial hepatic resection for hepatocellular carcinoma should be restricted to patients with well-compensated cirrhosis (Child's A class). Acceptable parameters include a single lesion not exceeding 5 cm, normal levels of bilirubin, and absence of portal hypertension. Liver transplantation is the best definitive treatment for HCV-infected patients who have small, localized HCC (solitary lesion not greater than 5 cm, or no more than 3 lesions, none of which are greater than 3 cm). Limitations of liver transplantation as a therapy for HCC are the scarcity of donor organs and the prolonged waiting time during which continued tumor growth occurs. Living donors can reduce waiting time and increase the number of patients treatable by transplantation. Chemoembolization and local ablation therapies have not been shown to confer survival benefits as primary treatments for HCC. The potential benefit of these procedures in controlling tumor growth to "bridge" patients to liver transplantation must be further investigated. Similarly, systemic chemotherapy and hormonal therapy do not generally produce a survival advantage. However, recent studies that used octreotide and combination doxorubicin/cisplatin/5-FU/interferon appear to be promising.