Objective To evaluate the value of methylated Septin9 (mSEPT9) in the diagnosis and postoperative recurrence/metastasis monitoring of colorectal cancer. Methods A total of 76 patients with colorectal cancer who were hospitalized in Beijing Anorectal Hospital (Beijing Erlonglu Hospital) and positive for mSEPT9 before operation from January to December in 2020 were collected. Nineteen patients who were still positive for mSEPT9 at one week after operation were selected as the msept9 positive group, and 57 patients whose mSEPT9 became negative were selected as the msept9 negative group. The clinicopathological features and postoperative recurrence and metastasis of the two groups were analyzed and compared. Results There were significant differences in lymph node metastasis rate, vascular or nerve infiltration and clinical staging between the mSEPT9 positive group and the mSEPT9 negative group (P=0.024, P=0.009, P=0.009). There was no significant difference in age, gender, tumor location, degree of tumor differentiation, and tumor invasion depth (T stage), P>0.05. Two patients in the mSEPT9 positive group had liver metastases after operation, and there were no cases of metastasis or recurrence in the mSEPT9 negative group (P=0.024). Conclusion The mSEPT9 can be used as a potential tumor marker for the diagnosis of colorectal cancer and the monitoring of postoperative treatment effect, and more attention should be paid to patients who are still positive for mSEPT9 after surgery.