Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide. The disease is predominant in Asia and Africa, but its incidence is steadily increasing throughout the rest of the world . Most HCC develop in patients with a history of chronic hepatitis or cirrhosis in which there is continuous inflammation and regeneration of hepatocytes. Unlike other solid malignancies, the coexistence of inflammation and cirrhosis makes the early diagnosis and prognostic assessment of HCC much more difficult. This complication highlights the need to identify valuable biomarkers for the diagnosis and treatment of HCC.
The proliferation and survival of cancer cells require a process called oncogene addiction, which is the activation of specific oncogenes and inactivation of specific tumor suppressors, such as Rb1 in retinoblastoma  and BRCA1 in breast cancer . However, no specific oncogene addictions have been observed in HCC, which is a complex disease with a variety of underlying pathogenic anomalies caused by multiple risk factors. The lack of ideal biomarkers for HCC diagnosis, prognosis, and therapy has posed a major challenge to HCC management.
With advances in the understanding of tumor biology, interest in identifying molecular biomarkers of HCC has increased. Over the last decade, a number of new cutting-edge technologies such as next-generation sequencing [4, 5] and microarray technologies [6–8] have emerged, leading the search for biomarkers into a new era of “omics” [9, 10]. Using these technologies, it is now quite easy to examine a whole tumor genome (including copy number variations, loss of heterogeneity, aneuploidy, single nucleotide polymorphism) [11–14], transcriptome [15, 16], proteome [17, 18], epigenome [19, 20], metabolome [21–23], and miRNA profile [24, 25], and the analysis of tens of thousands of molecular targets has become affordable and operable. Currently, numerous circulating markers and tissue markers have been identified [17, 26–30]; however, few biomarkers are acceptable for clinical utility because of their low predictive accuracy and/or high cost. Here, we provide an up-to-date review of the biomarkers that are used for early diagnosis, prognosis, and personalized treatment of HCC.