Objective HCC is one of many malignant tumors. The HCC markers are most urgently necdad. But the currently available markers lack sensitivity and specificity. A number of novel candidate markers have recently been introduced. Methods We performed a review of the literature of traditional and novel serum markers for hepatocellular cancer. Results Several promising new HCC markers have rencently been identified. They include single protein, complex proteomics features, and tumor-specific autoantibodies.The excitement about the new markers is tempered by the realization that none of them have yet met the most stringent criteria defined by the Early Detection Research Network (EDRN). Conclusion A new generation of HCC serum markers awaits validation in properly controlled clinical studies.