Hepatocellular carcinoma (HCC) is the most frequent tumour derived from the malignant transformation of hepatocytes. It is well established that cancer is a disease of the genome and, as in other types of solid tumours, a large number of genetic and epigenetic alterations are accumulated during the hepatocarcinogenesis process. Recent developments using comprehensive genomic tools have enabled the identification of the molecular diversity in human HCC. Consequently, several molecular classifications have been described using different approaches and important progress has been made particularly with the transcriptomic, genetic, chromosomal, miRNA and methylation profiling. On the whole, all these molecular classifications are related and one of the major determinants of the identified subgroups of tumours are gene mutations found in oncogenes and tumour suppressors. However, the full understanding of the HCC molecular classification requires additional comprehensive studies using both genomic and pathway analyses. Finally, a refinement of the molecular classification of HCC, taking into account the geographical and genetic diversity of the patients, will be essential for an efficient design of the forthcoming personalized clinical treatments.