Objective      To identify the differential proteins in plasma of hepatocellular carcinoma (HCC) with RP-HPLC and matrix-assisted laser desorption ionzation time of flight mass spectrum (MALDITOF MS).        Methods      Plasma from 8 healthy volunteers and 9 HCC patients were collected. After depleting six plasma proteins of the highest abundance by the Multiple Affinity Removal System (MARS) Technologies from Agilent

plasma were subjected to RP-HPLC and the molecular weight of differentially expressed protein was identified by MALDITOF MS.        Results      The proteins whose molecular weight are between 15×10

3

and 50×10

3

in plasma from healthy subjects were more than in

hepatocelluar carcinoma patients

while the proteins whose molecular weight are between 50×10

3

and 90×10

3

in plasma from healthy subjects are less than in hepatocelluar carcinoma patients.       Conclusion      RP-HPLC/TOF MS based plasma proteome analysis can be useful in detecting protein expression alteration resulting from the carcinogenesis and development of HCC and new discovered biomarkers might be an aid in the diagnosis of HCC.