Background: Colorectal cancer (CRC) represents a third leading cause of cancer-related death worldwide. The reliable diagnostic biomarkers for detecting CRC at early stage is critical for decreasing the mortality.Method: A conjunctive lipidomic approach was employed to investigate the differences in plasma lipid profiles of CRC patients (n = 101) and healthy volunteers (n = 52). Based on UHPLC-Q-TOF MS and UHPLC-QQQ MS platforms, a total of 236 lipids were structurally detected. Multivariate data analysis was conducted for biomarkers discovery.Results: A total of 11 lipid species, including 1 Glycerophosphoethanolamine (PE), 3 ethanolamine plasmalogens (PlsEtn), 1 plasmanyl glycerophosphatidylethanolamine (PE-O), 3 fatty acids (FFA), 1 Fatty acid ester of hydroxyl fatty acid (FAHFA) and 2 Diacylglycerophosphates (PA) were identified to distinguish the CRC patients at early stage from healthy controls. In addition, these potential lipid biomarkers achieved an estimated AUC=0.981 in a validation set for univariate ROC analysis.Conclusion: By combining Q-TOF MS and QQQ MS analysis, the 11 lipids exhibited good performance in differentiating early-stage CRC and healthy control. This study also demonstrated that lipidomics is a powerful tool in discovering new potential biomarkers for cancer diagnosis.