 Hepatitis B and C infections cause hepatocellular carcinoma, HCC, by replicating in hepatocytes. Inflammation, cell death and proliferation result. HCC is the second leading cause of death from cancer worldwide, with a rapidly increasing incidence in the United States, especially among drug users due to the opioid epidemic. The liver plays a key role in maintaining adequate glucose levels and carrying nutrients and toxins to be filtered, such as urea. The liver also secretes bile, which is used to solubilize fat for absorption and utilization. A healthy liver has a brown, smooth surface. The liver cells are organized into lobules, where the portal vein, hepatoc artery and bile duct are arranged hexagonally around the central vein to make the portal triad. Hepatocytes in an assignments are arranged in three zones. Viral zone I is nearest to the entering vascular supply. It gets the most oxygenated blood, making it less sensitive to a schemic injury, but more susceptible to viral hepatitis. Normal hepatocytes are arranged in single cell thick plates separated by sinusoids. In HCC, plates are 2 plus cells thick and cell nuclei are enlarged and convoluted. Large tumor nodules are separated by thick fibrous bands shown as blue webbing. HBV and HCV can cause genome mutations, leading to tumor gene suppression, oncogene activation and chromosomal rearrangements. These mechanisms increase the risk of HCC. However, the highest HCC risk is from co-infection of HBV with HCV, HDV, or HIV and is secondary to cirrhosis, which increases cell turnover. Both HBV and HCV infections can be silent, but symptoms including creased serum transaminous enzymes, jaundice, and flu-like ailments. Chronic HBV can remain dormant until late-stage liver disease. Co-infection with HDV causes progression of fibrosis and cirrhosis, as evident by the portal bridging. This co-infection increases risk of early onset HCC. Increasing infection from hepatitis is important in decreasing the risk for liver cancer. This can be achieved through increasing hygiene standards and vaccination programs. The U.S. Food and Drug Administration named the hepatitis B vaccine the first anti-cancer vaccine, which is now recommended for all children and those at risk of infection. To prevent HCV, avoid sharing blood or bodily fluids with those affected. Using safe sex and avoidance of needle-sharing is also key.