Objective: To analyze the short-term efficacy of complete mesocolic excision (CME) in the treatment of senile colon cancer and its effect on serum tumor markers. Methods: A total of 165 elderly patients with colon cancer who were admitted to our hospital from September 2016 to September 2019 were randomly divided into two groups: 82 patients in the reference group were treated with traditional radical surgery, and 83 patients in the experimental group were treated with CME. The surgical indexes, serum tumor markers, complication rate and recurrence rate within 6 months were compared between the two groups. Results: The operation time of the experimental group was longer than that of the control group (P<0.05); the intraoperative bleeding volume of the experimental group was significantly lower than that of the reference group, the first postoperative exhaust time and hospitalization time of the experimental group were significantly shorter than that of the reference group, and the number of lymph node dissections in the experimental group significantly higher than the reference group (P<0.05). The levels of serum CA199, SF, CEA, and CA125 in the experimental group were significantly lower than those in the reference group at 1 month after operation. The incidence of complications in the experimental group (2.41%) and the recurrence rate within 6 months (3.61%) were significantly higher than those in the reference group (13.41%, 23.17%) low (P<0.05). Conclusion: CME can effectively improve condition of elderly colon cancer patients in the short term, suppress high expression of serum tumor markers, reduce incidence of complications and recurrence rate, and has a significant effect.