Background: Early diagnosis will significantly improve the survival rate of colorectal cancer (CRC); however, the existing methods for CRC screening were either invasive or inefficient. There is an emergency need for novel markers in CRC’s early diagnosis. Serum proteomics has gained great potential in discovering novel markers, providing markers that reflect the early stage of cancer and prognosis prediction of CRC. In this paper, the results of proteomics of CRC studies were summarized through a meta-analysis in order to obtain the diagnostic efficiency of novel markers.Methods: A systematic search on bibliographic databases was performed to collect the studies that explore blood-based markers for CRC applying proteomics. The detection and validation methods, as well as the specificity and sensitivity of the biomarkers in these studies, were evaluated. Newcastle- Ottawa Scale (NOS) case-control studies version was used for quality assessment of included studies. Results: Thirty-four studies were selected from 751 studies, in which markers detected by proteomics were summarized. In total, fifty-nine proteins were classified according to their biological function. The sensitivity, specificity, or AUC varied among these markers. Among them, Mammalian STE20-like protein kinase 1/ Serine threonine kinase 4 (MST1/STK4), S100 calcium-binding protein A9 (S100A9), and Tissue inhibitor of metalloproteinases 1 (TIMP1) were suitable for effect sizes merging, and their diagnostic efficiencies were recalculated after merging. MST1/STK4 obtained a sensitivity of 68% and a specificity of 78%. S100A9 achieved a sensitivity of 72%, a specificity of 83%, and an AUC of 0.88. TIMP1 obtained a sensitivity of 42%, a specificity of 88%, and an AUC of 0.71. Conclusion: MST1/STK4, S100A9, and TIMP1 showed excellent performance for CRC detection. Several other markers also presented optimized diagnostic efficacy for CRC early detection, but further verification is still needed before they are suitable for clinical use. The discovering of more efficient markers will benefit CRC treatment.