Hepatocellular carcinoma (HCC) is increasing in frequency the USA. Age-adjusted incidence, hospitalization, and mortality rates have doubled over the past two decades. There are striking differences in the incidence of HCC related to age, gender, race, and geographic region. Although it remains an affliction of the elderly (mean age 65), there has been a considerable shift toward younger cases. There is a birth cohort effect with those born after 1945. Men are affected three times more frequently than women, Asians two times more than African American and Hispanic people, who are affected two times more often than Caucasians. However, the recent increase has disproportionately affected Caucasian (and Hispanic) men between ages 45 and 65. Hepatitis C virus (HCV) infection acquired 2–4 decades ago explains at least half of the observed increase in HCC; HCV-related HCC is likely tocontinue to increase for the next decade. A variable but significant proportion of cases (15–50%) do not have evidence for the risk factors of either viral hepatitis or heavy alcohol consumption. Insulin resistance syndrome manifesting as obesity and diabetes is emerging as a risk factor for HCC in the USA and may operate through the formation of non-alcoholic fatty liver disease (NAFLD); however, its effect on the current trend in HCC remains unclear. While there has been a small recent improvement in survival, it remains generally dismal (median 8 months). Population-based data in the USA indicate low application rate of HCC potentially curative therapy and marked regional differences.