Objective: To analyze the expression level of multi-tumor markers in laparoscopic drainage of patients with colorectal cancer and its correlation with the disease. Methods: A total of 76 patients with colorectal cancer who underwent surgical treatment in Affiliated Hospital of Jiangnan University from January to December 2019 were selected and divided into group I (T1 and T2 patients) and group II (T3 and T4 patients) according to the cancer staging of the patients. The differences of tumor markers between the 2 groups were compared, and the differences of tumor markers with or without lymphatic metastasis in patients with colorectal cancer before and after surgery were analyzed. Results: The CA50, CA125, CA242, CA19-9, and CEA level in group I were significantly lower than those in group II in line with the detection result, and the differences were statistically significant (P<0.05). In addition, in patients with colorectal cancer who had no lymphatic metastasis after operation, the corresponding tumor marker indexes decreased significantly, while the expression of each tumor marker in patients with lymphatic metastasis increased compared with that before the surgery (P<0.05). Conclusion: The detection of tumor markers can reflect the progress of colorectal cancer and provide reference for clinical practice.