Despite of the advances in clinical imaging and applied research in proteomic biomarkers, liver cancer, especially hepatocellular carcinoma remains detected at the very late and advanced stages when curable treatments are unavailable and ineffective. In this regard, there are still huge unmet medical needs in developing and clinically validating those high-potential protein biomarkers preferably in liquid biopsy samples. This review provides a glimpse of emerging biomarkers together with detection tools and techniques which are potentially commercially available to the markets. We also discuss several diagnostic biomarkers having therapeutic potential for developing first-in-class medicines.