Primary hepatocellular carcinoma (HCC) is an important cause of death in patients with chronic liver disease and in carriers of hepatitis B virus. Because of its relative frequency in certain geographic areas, such as Asia and sub-Saharan Africa, mass screening programs have been instituted to implement secondary prevention. It is believed that early diagnosis provides the best chance of successful surgical resection and hopefully prolonged survival. Although a number of serological and imaging tests are available, the most cost-effective modality is serum alphafetoprotein (AFP) and real-time ultrasound (USS) used together. The current recommendation is recognition of high-risk groups (cirrhosis, chronic active hepatitis, and chronic hepatitis B carriers) and provision of AFP and USS testing at 3 to 6 months intervals, with recourse to fine-needle aspiration biopsy and celiac angiography for individuals who test positive with either test.