Although rare in Canada and the United States, hepatocellular carcinoma (HCC) ranks as the eighth most common cancer in the world. High-risk regions are East and Southeast Asia, and sub-Saharan Africa. Independent of race and geography, rates in men are at least two to three times those in women; this sex ratio is more pronounced in high-risk regions. Rates of HCC in the United States have increased by 70% over the past two decades. Registry data in Canada and Western Europe show similar trends. In contrast, the incidence of HCC in Singapore and Shanghai, China, both high-risk regions, has declined steadily over the past two decades. Among white and black Americans, there is an inverse relationship between social class status and HCC incidence. Chronic infection by the hepatitis B virus (HBV) is by far the most important risk factor for HCC in humans. It is estimated that 80% of HCC worldwide is etiologically associated with HBV. In the United States, although the infection rate in the general population is low, HBV is estimated to account for one in four cases of HCC among non-Asians. Chronic infection by the hepatitis C virus is another important risk factor for HCC in the United States; however, this virus is believed to play a relatively minor role in the development of HCC in Africa and Asia. Dietary aflatoxin exposure is an important codeterminant of HCC risk in Africa and parts of Asia. In Canada and the United States, excessive alcohol intake, cigarette smoking and oral contraceptive use in women also are risk factors for HCC.