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To investigate the correlation between postoperative serum metastasis-associated in colon cancer-1 (MACC1) and prognosis of colon cancer patients after laparoscopic complete mesocolic excision (CME).A total of 280 colon cancer patients undergoing laparoscopic CME were included. The 40-month disease-free survival, progression-free survival, and overall survival were calculated.Immunohistochemical staining, western blotting, and quantitative real-time polymerase chain reaction results showed that the MACC1 expression in cancer tissues was significantly higher than adjacent tissues (P<0.05). Compared with the small interfering RNA-negative control group, the tumor weight, tumor volume, and tumor number were all significantly decreased after treatment with small interfering RNA-MACC1 (P<0.05). Survival analysis showed that compared with the low MACC1 group, the disease-free survival (χ2=30.095, P<0.001), progression-free survival (χ2=50.027, P<0.001), and overall survival (χ2=53.861, P<0.001) in the high MACC1 group all decreased significantly.Postoperative serum MACC1 has a potential value for evaluating the prognosis of patients undergoing laparoscopic CME.