Primary liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide and the third most common cause of cancer mortality. HCC has several interesting epidemiologic features including dynamic temporal trends; marked variations among geographic regions, racial and ethnic groups, and between men and women; and the presence of several well-documented environmental potentially preventable risk factors. Moreover, there is a growing understanding on the molecular mechanisms inducing hepatocarcinogenesis, which almost never occurs in healthy liver, but the cancer risk increases sharply in response to chronic liver injury at the cirrhosis stage. A detailed understanding of epidemiologic factors and molecular mechanisms associated with HCC ultimately could improve our current concepts for screening and treatment of this disease.