Hepatocellular carcinoma (HCC) is a highly malignant tumor and is the most common cause of death in patients with underlying liver cirrhosis. The main risk factor for development of HCC is liver cirrhosis. Because of the increasing frequency of nonalcoholic steatohepatitis, the incidence of HCC is also expected to considerably rise in Western countries in upcoming years. Identification and surveillance of patients at risk is crucial because curative treatment approaches can only be applied at early stages of the disease. Due to underlying liver cirrhosis, therapeutic strategies are limited and require intense interdisciplinary cooperation and multimodal approaches. However, a strong morphological and genetic heterogeneity of HCC remains a major challenge for development of new treatment modalities and demands personalized precision medicine approaches in order to improve patient outcome.