Objective: To explore the effects of lobaplatin perfusion on serum tumor markers during colorectal cancer surgery. Methods: According to random number table method, 60 patients with colorectal cancer undergoing surgical treatment in the hospital were divided into treatment group (n=30) and control group (n=30) between January 2022 and June 2024. The control group was given intraoperative intraperitoneal hyperthermic perfusion of raltitrexed, while treatment group was given intraperitoneal hyperthermic perfusion of lobaplatin (50 mg/m2⁾ + raltitrexed. The levels of serum carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 724 (CA742) in the two groups were compared before surgery and at 1 month, 3 months, 6 months, 9 months and 12 months after surgery. The differences in recurrence, recurrence-free survival time and overall survival time between the two groups were followed up at 1 year after surgery. The occurrence of adverse reactions within 1 month after intraperitoneal hyperthermic perfusion in the two groups was recorded. Results: At 1 month, 3 months, 6 months, 9 months and 12 months after surgery, levels of CEA, CA125, CA19-9 and CA724 were decreased in both groups (P<0.05), which were lower in treatment group than control group (P<0.05). After 1 year of follow-up, recurrence rate in treatment group was lower than that in control group, recurrence-free survival time and overall survival time were longer than those in control group (P<0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P>0.05), and all adverse reactions were relieved after symptomatic treatment. Conclusion: Lobaplatin perfusion during colorectal cancer surgery can effectively decrease levels of postoperative serum tumor markers, reduce recurrence and prolong survival time, with good safety.