Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world. The major etiologic risk factors include toxins (alcohol, aflatoxin B(1)), hepatitis B and C virus infection as well as various inherited metabolic disorders. The prognosis of HCC patients is generally very poor with a 5-year survival rate of less than 5%. The diagnosis is based on biochemical and imaging tests as well as histology. Therapeutic strategies include surgery (resection or liver transplantation) and non-surgical interventions, such as percutaneous ethanol injection or radiofrequency thermal ablation as well as transarterial embolization or chemoembolization. Radio- or chemotherapy are mostly ineffective. Therefore, the development and evaluation of novel HCC treatment strategies as well as the implementation of existing and the development of new measures to prevent HCC are of utmost importance. The better understanding of the clinical and molecular pathogenesis of HCC should lead to improved diagnostic, therapeutic and preventive strategies with the aim to reduce the incidence of HCC, one of the most devastating malignancies worldwide.