Abstract: Objective To explore the preventive effect of different combined drug interventions based on dexmedetomidine on remifentanil-induced hyperalgesia (RIH). Methods A total of 90 patients undergoing laparoscopic cholecystectomy under general anesthesia were randomly divided into control group, dexmedetomidine combined with dezocine group (dezocine group), and dexmedetomidine combined with oxycodone group (oxycodone group), with 30 cases in each group. Anesthesia was induced with 0.03 mg/kg of midazolam, 2 mg/kg of propofol, cisatracurium 0.2 mg/kg and 1 μg/kg of remifentanil in all three groups. At 5 min before anesthesia induction, 0.7 g/kg dexmedetomidine was injected intravenously in all three groups, and the infusion was completed within 30 min. Dezocine group and oxycodone group received intravenous dezocine (0.1 mg /kg) or oxycodone (0.1 mg /kg) 30 min before the end of surgery, respectively. Normal saline of equal volume was injected intravenously in the control group. VAS scores at 30 min and 1, 6, 12, 24 h after surgery and Ramsay scores at 30, 60, 90 min after surgery were recorded for each group, and the rate of supplementary analgesics and adverse reactions were observed. Results VAS scores of both dezocine group and oxycodone group were lower than that of the control group at each time point after operation (P<0.05). VAS scores at 30 min, 1 h, 12 h and 24 h after operation were significantly lower in the dezocine group than in the oxycodone group (P<0.05). Ramsay scores in both dezocine group and oxycodone group were lower than that in the control group (P<0.05). There was no statistically significant difference in Ramsay score between the dezocine group and the oxycodone group at each postoperative time point (P>0.05). The rate of supplementary analgesics in the dezocine group and oxycodone group was lower than that in the control group (P<0.05). There was no significant difference in the rate of supplementary analgesics between the dezocine group and the oxycodone group (P>0.05). The incidence of dizziness, nausea and vomiting in the dezocine group and the oxycodone group was higher than that in the control group (P<0.05). The incidence of dizziness, nausea and vomiting in the oxycodone group was higher than that in the dezocine group (P<0.05). Conclusions Compared with dexmedetomidine combined with oxycodone, dexmedetomidine combined with dezocine is more effective in relieving RIH, with fewer adverse reactions and higher analgesic satisfaction.