Objective: To investigate the application of CT enhancement in the staging of colon cancer and the diagnostic value of combined serum CEA, CA199, CA724 and microRNA-21 in benign and malignant lesions. Methods: 85 patients with colon cancer diagnosed in our hospital from March 2018 to March 2022 were included in the observation group, and 85 patients with colon benign tumors in the same period were included in the control group. Based on the pathological results as the gold standard, the diagnostic value of CT enhanced staging in T, N, M staging of colon cancer patients was analyzed, and compared the serum CEA, CA199, CA724, microRNA-21 levels between the two groups. At the same time, evaluated the value of CT enhancement and serum CEA, CA199, CA724, microRNA-21 alone and joint in the diagnosis of benign and malignant lesions of colon cancer. Results: The accuracy of CT enhanced T staging was 88.2%, with high consistency (Kappa value=0.812); The accuracy rate of CT enhanced N staging was 63.5%. with general consistency (Kappa value=0.449); The accuracy rate of CT enhanced M staging was 90.6%, with high consistency (Kappa value-0.739). The levels of serum CEA, CA199, CA724 and microRNA-21 in the observation group were higher than those in the control group(P<0.05). The analysis results of the receiver operation characteristic curve(ROC) of the subjects showed that the area under the ROC curve (AUC) (0.95CI) of CT enhancement and serum CEA, CA199, CA724 and microRNA-21 in the diagnosis of benign and malignant lesions of colon cancer were 0.783, 0.722 (0.497~0.944), 0.694 (0.475~0.916), 0.704 (0.434~0.977), 0.687 (0.393~0.967) and 0.917 (0.829~0.982), respectively. 75 patients with malignant colon cancer were examined by CT enhancement and joint with serum CEA, CA199, CA724 and microRNA-21. The diagnostic sensitivity was 88.2%, specificity was 90.6%, and accuracy was 89.4%. Conclusion: CT enhancement can be applied to the staging of colon cancer,and the joint of CT enhancement with serum CEA, CA199, CA724 and microRNA-21 can effectively and accurately determine the benign and malignant lesions of colon cancer, which has important clinical significance in improving the diagnosis of colon cancer. [ABSTRACT FROM AUTHOR]