In this article, the epidemiology of hepatocellular carcinoma (HCC), risk factors for the development of HCC, and how these factors affect the decision about whether an individual should or should be entered into a screening program are considered. The factors determining the risk for HCC include age, male gender, and the nature of the underlying liver disease. In particular, cirrhosis is associated with a significant risk for HCC. However, in hepatitis B HCC also occurs in noncirrhotic liver. Decision analysis can be used to identify patients at greatest risk for HCC and who might be candidates for screening. Screening itself should be developed in a programmatic manner to ensure that appropriate target populations are identified, that appropriate screening tests are chosen, and that appropriate recall and enhanced follow-up are instituted for patients who have positive screening test results. Screening should be by ultrasonography at 4-to 12-month intervals. Patients with abnormal screening tests require additional investigation using computed tomography scanning, magnetic resonance imaging, or liver biopsy. Negative results do not exclude the possibility of cancer and further follow-up is necessary.