Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.

HCC most commonly occurs in those with chronic liver disease especially those with cirrhosis or fibrosis, which occur in the setting of chronic liver injury and inflammation. HCC is rare in those without chronic liver disease. Chronic liver diseases which greatly increase the risk of HCC include hepatitis infection such as (hepatitis B, C or D), non-alcoholic steatohepatitis (NASH), alcoholic liver disease, or exposure to toxins such as aflatoxin, or pyrrolizidine alkaloids. Certain diseases, such as hemochromatosis and alpha 1-antitrypsin deficiency, markedly increase the risk of developing HCC. The five-year survival in those with HCC is 18%.

As with any cancer, the treatment and prognosis of HCC varies depending on tumor histology, size, how far the cancer has spread, and overall health of the person.

The vast majority of HCC cases and the lowest survival rates after treatment occur in Asia and sub-Saharan Africa, in countries where hepatitis B infection is endemic and many are infected from birth. The incidence of HCC in the United States and other higher income countries is increasing due to an increase in hepatitis C virus infections. The incidence of HCC due to NASH has also risen sharply in the past 20 years, with NASH being the fastest growing cause of HCC. This is thought to be due to an increased prevalence of NASH, as well as its risk factors of diabetes and obesity, in higher income countries. It is more than three times as common in males as in females, for unknown reasons.

Most cases of HCC occur in people who already have signs and symptoms of chronic liver disease. They may present with worsening symptoms or without symptoms at the time of cancer detection. HCC may present with non-specific symptoms such as abdominal pain, nausea, vomiting, or feeling tired. Some symptoms that are more closely associated with liver disease include jaundice, abdominal swelling due to fluid in the abdominal cavity, easy bruising from blood clotting abnormalities, loss of appetite, unintentional weight loss, abdominal pain, nausea, vomiting, or feeling tired.

Since HCC mostly occurs in people with cirrhosis of the liver, risk factors generally include factors which cause chronic liver disease that may lead to cirrhosis. Certain risk factors are more highly associated with HCC than others. For example, while heavy alcohol consumption is estimated to cause 60–70% of cirrhosis, the vast majority of HCC occurs in cirrhosis attributed to viral hepatitis (although there may be overlap). Recognized risk factors include:

The significance of these risk factors varies globally. In regions where hepatitis B infection is endemic, such as southeast China, hepatitis B is the predominant cause. In populations largely protected by hepatitis B vaccination, such as the United States, HCC is most often linked to causes of cirrhosis such as chronic hepatitis C, obesity, and excessive alcohol use.

Certain benign liver tumors, such as hepatocellular adenoma, may sometimes be associated with coexisting malignant HCC. Evidence is limited for the true incidence of malignancy associated with benign adenomas; however, the size of hepatic adenoma is considered to correspond to risk of malignancy and so larger tumors may be surgically removed. Certain subtypes of adenoma, particularly those with β-catenin activation mutation, are particularly associated with increased risk of HCC.