Objective To observe the effect of dezocine combined with dexmedetomidine on reducing adverse reaction of hyperthermic intraperitoneal chemotherapy (HIPEC) after intestinal operation, and provide reference for clinical application. Methods A total of 80 patients with HIPEC were divided into intervention group and routine group according to different methods of sedation and analgesia. On the basis of routine sedation and analgesia，the 5 mg muscle injection of dizocine was given for patients in intervention group, and normal saline 48 mL+ dexmedetomidine 200 μg were continuously pumped at 0.3 μg/(kg·h) until the end of the HIPEC. The occurrence of adverse reactions in HIPEC was compared between the two groups of patients. Results Results showed that the heart rates [(83.34±8.25) times/min vs. (90.11±10.69) times/ min] and body temperature [(37.33±0.42)℃ vs. (37.95±0.51)℃] were significantly lower in the intervention group than those of routine group (P＜0.01). The incidence rates of nausea, vomiting, pain and irritability were significantly lower in the intervention group than those of routine group (P＜0.05). Conclusion Dezocine combined with dexmedetomidine can significantly reduce the incidence of adverse reactions in patients undergoing HIPEC after intestinal surgery.