Abstract: Objective: Discovery of biomarkers by use of SELDI-TOF mass spectrometry in the serum from hepatocellular carcinoma and healthy people. Methods: Twenty-five patients with hepatocellular carcinoma free of any therapy, 25 patients receiving the interpose chemotherapy and 50 healthy people were tested by Weak cationic exchanger (WCX2) protein chip and surface enhanced laser desorption ionization-time of flight-mass-spectrometry of Ciphergen Inc. Results: At the different M/Z value range, seven proteins were obviously different in the group of the patients with hepatocellular carcinoma without recieving any therapy , the patients with hepatocellular carcinoma recieving the interpose chemotherapy and the healthy people. Through searching database, these seven proteins might be Galanin related peptide, Pro-neuregulin-4 protein, small inducible cytokine A15 precursor, 9 kDa protein, CSL-zincfinger protein 1, mitochondrial hinge protein, actin related protein, respectively. Conclusion: These differential proteins could be biomarkers of hepatocellular carcinoma in the serum.