Hepatocellular carcinoma (HCC) is the fifth most common cancer, the third most common cause for cancer death in the world, a major cause of death in patients with chronic hepatitis C virus infection, and responsible for approximately one million deaths each year. Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of HCC. The incidence of HCC is expected to increase in the next two decades, largely due to hepatitis C infection and secondary cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. Potential preventive strategies in the development of HCC are being recognized. The natural history of HCC is highly variable and the clinical management choices for HCC can be complex, hence patient assessment and treatment planning have to take the severity of the nonmalignant liver disease into account. This review summarizes the inter-relationship between HCV and liver carcinogenesis.