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No distinctive biomarkers capable of discriminating between ulcerative colitis (UC) and Crohn's disease (CD) have yet been found. In this study, we aimed to discover these biomarkers by using advanced label-free quantification technology for proteomes.Biomarker protein expressions of colonic tissues of Korean IBD patients and controls were determined using label-free quantification to compare the protein profiles of colonic mucosa in three individuals with normal colonic tissue, four patients with UC, three with CD and two with inflammatory polyps related to UC. A computational framework and tools for discovery-based liquid chromatography-tandem mass spectrometry proteomics was applied to draw the biomarkers.In total, 339 proteins were identified in normal sample group, 217 and 283 proteins in active and inactive UC, 345 and 366 proteins in active and inactive CD and 392 proteins in inflammatory polyps related to UC, respectively. The findings were reproducible. A Corra analysis led to the discovery of 27 potential biomarkers in UC, 37 biomarkers relevant to CD and 11 proteins commonly associated with IBD. Three novel proteins, PRG2, LCP1 and PSME1 were identified as biomarkers signifying active CD.This is the first study to apply label-free quantification for discovering biomarkers in patients with different types and stages of IBD, providing additional insights for revealing the molecular pathogenesis of IBD as well as protein biomarkers of IBD predicting responses to treatment.