The epidemiology of hepatocellular carcinoma (HCC) has changed in the United States in the past several decades. The first study of my thesis was a population based study to evaluate HCC with regard to the incidence rates, etiology, treatment, survival and cause of death in Olmsted County between 1976 and 2008. Clinical information was abstracted from the medical records. The age- and sex-adjusted incidence rates were 3.6, 3.8, and 6.9 per 100,000 person-years for the first (1976-1990), second (1991-2000), and third periods (2001-2008), respectively. Alcohol was the most common risk factor in the first and second periods and chronic hepatitis C (HCV) in the third. The median survival improved from 2 and 6 months in the first two periods to 9 months in the third (p=0.01), in part due to increased surveillance (p<0.01). In our next study, we performed a hospital based cohort study to evaluate risk factors for HCC, the proportion of cases detected via surveillance, tumor characteristics, treatment approaches, and overall patient survival in a referral center. The study included all patients diagnosed with HCC at the Mayo Clinic, Rochester, MN, from 2007 to 2009 (n=460). Hepatitis C virus (HCV, 36%), alcohol use (29%), and nonalcoholic fatty liver disease (NAFLD, 13%) were the most common risk factors for HCC. HCC was detected during surveillance in 31% of patients. Patients diagnosed with HCC during surveillance had less-advanced disease, were more likely to be eligible for potentially curative treatments, and had increased survival times (P<0.001). In the last study, we investigated about the prevalence or effects of cirrhosis in patients with HCC from viral hepatitis. The prevalence of histologic cirrhosis was 88% among patients with HBV infection and 93% among those with HCV infection (P=0.46). When the most inclusive criteria for cirrhosis were applied, cirrhosis was present in 94% of patients with HBV and 97% with HCV (P=0.24).