Background: M2-pyruvate kinase (M2-PK) is a tumor growth key regulator and plays a crucial role in tumor metabolism and can dynamically regulate aerobic glycolsis. Notwithstanding, the colonoscopy is the gold standard for early detection of colorectal cancer (CRC), the acceptance of this invasive technique is low. Aim of the work: to assess the diagnostic value of plasma M2-PK in Egyptian patients with CRC. Methods: we measured the plasma M2-PK using Enzyme-linked immunosorbent assay in CRC patients and comparing these levels with those obtained from patients with functional bowel disorders (FBD), inflammatory bowel disease (IBD),colorectal polyp and apparently healthy individuals and to detect its sensitivity and specificity. Results: the value of plasma M2-PK level was higher in CRC patients, 15.22 U/ml than other groups. Average plasma M2-PK was 6.78, 5.28, 2.25 and 2.1 U/ml among colorectal polyp, IBD, FBD patients and normal individuals respectively. The plasma M2-PK can be used in differentiating between CRC and normal individual with  83.33% sensitivity, 100% specificity at area under the curve (AUC) 0.949  with cut-off >6U/ml. Also, it can be used to discriminate between colorectal polyp and CRC patients at cut-off level of >10.6 U/mL with 75.5% sensitivity and 87.5% specificity and to differentiate between FBD and organic colonic lesions at cut-off level >3 U/ml with 81.94% sensitivity and 83.3% specificity. Conclusion: plasma M2-PK was considerably elevated in CRC patients and may be used as non-invasive biomarker for CRC. Recommendation: future researches including a large and long-term follow-up studies are recommended.