The rising incidence of hepatocellular carcinoma (HCC) in the United States is of importance to all practitioners. Louisiana has one of the highest HCC related mortality rates in the United States. Our study reviews the experience with HCC at Tulane University Medical Center from 2003 to 2009 and compares our experience with the national experience. Our data shows that from 2003 to 2009, the number of new HCC cases seen at Tulane increased by 300%, paralleling reported national trends. Infection with the hepatitis C virus (HCV) leading to cirrhosis is the most common factor in the development of HCC. In addition, our data suggests that diabetes may play a role in the development of HCC. Our study confirms the rising incidence of HCC in Louisiana and provides strong support for the rapid implementation of statewide surveillance programs for the early detection of HCC in individuals at risk.