Abstract: Objective To study serum proteomic fingerprints of colorectal cancer during onset and progression and to screen tumor markers related to prognosis. Methods Serum from colorectal cancer patients, non-cancer patients, and healthy control were profiled using WCX ProteinChip or magnetic beads and analyzed by mass spectrometry. Results Seven protein peaks were found related to colorectal cancer. Several peaks were closely related to lymph node metastasis, distal organ metastasis and decreased after surgery. The diagnostic model composed of 3398.3、5477.1、8453.9 u can detect CEA negative colorectal cancer in 100%. Conclusion Protein fingerprinting technology (PFT) in conjunction with bioinformatics can significantly identify novel biomarkers in the serum of colorectal cancer patients with potential values for prognostic evaluation, detection of CEA negative colorectal cancer and changing its progression.