Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for HCC development are well defined and some of the steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these advances and the implementation of measures for early HCC detection as well as novel therapeutic strategies, the survival of patients with HCC has not significantly improved until recently. Therefore, early diagnosis and primary, as well as secondary, prevention are of paramount importance in order to reduce morbidity and mortality from HCC. New technologies, including gene expression profiling and proteomic analyses, should allow further elucidation of the molecular events underlying HCC development and identification of novel diagnostic markers as well as therapeutic and preventive targets.