Hepatocellular carcinoma (HCC) is an aggressive malignancy of the liver and occurs most often in the setting of chronic liver disease. The most common acquired causes for this are chronic viral hepatitis infections (mostly HBV and HCV), and alcohol. Other causes include nonalcoholic fatty liver disease-related nonalcoholic steatohepatitis, autoimmune liver disease, and biliary diseases. In addition, certain heritable diseases like hemochromatosis and α-1-antitrypsin deficiency can also lead to HCC. Therefore, prevention of HCC can be achieved by preventing and controlling these problems. For treatment, curative modalities are surgical resection and liver transplantation. However, most patients are not candidates for these surgical maneuvers, and outcomes are poor. New therapeutic developments have brought some improvement with both local and systemic disease control.