Hepatocellular carcinoma (HCC) is associated with liver disease, particularly cirrhosis and hepatitis B and C. HCC can be diagnosed clinically based on alpha fetoprotein and radiographic criteria or less commonly with biopsy. Patients on the transplant waiting list should continue to be screened to ensure they do not develop HCC while awaiting transplant. HCC can be associated with cutaneous features including dermatomyositis, pemphigus foliaceus, sign of Leser-Trelat, pityriasis rotunda, and porphyria cutanea tarda although these are not specific to HCC. Vaccination of infants reduces rates of development of hepatitis B virus infection and reduces incidence of HCC. Chemotherapy is difficult to administer in patients with HCC who often have associated poor liver function. This chapter describes epidemiology, risk factors, anatomy, pathology, clinical presentation, prognostic factors, natural history, staging, and treatment paradigm of HCC.