Objective To observe the effect of nalbuphine and parecoxib therapy attenuates remifentanil‑induced hyperalgesia (RIH) after surgery. Methods A total of 100 patients who were scheduled for laparoscopic hysterectomy were selected. According to the random number table method, they were divided into four groups: a sufentanil group (group S, n=23), which was administered with 0.30 μg/kg sufentanil during anesthesia induction followed by intermittent addition of sufentanil during surgery for anesthesia maintenance; a remifentanil group (group R, n=25), which received remifentanil at 2.0 μg/kg during anesthesia induction followed by continuous infusion of remifentanil at 0.30 μg∙kg−1∙min−1 for anesthesia maintenance during surgery; a nalbuphine+remifentanil group (group NR, n=23), which was administered with 0.1 mg/kg nalbuphine 15 min before anesthesia induction, then received 2.0 μg/kg remifentanil during anesthesia induction, before continuous infusion of remifentanil at 0.30 μg∙kg−1∙min−1 for anesthesia maintenance during surgery; and a nalbuphine+parecoxib+remifentanil group (group NPR, n=25), which received 0.05 mg/kg nalbuphine and 40 mg parecoxib 15 min before anesthesia induction, then received 2.0 μg/kg remifentanil during anesthesia induction, before continuous infusion of remifentanil at 0.30 μg∙kg−1∙min−1 for anesthesia maintenance during surgery. All patients received patient‑controlled analgesia pump for postoperative analgesia. The Numerical Rating Scale (NRS) scores at postoperative 1, 3, 6, 12, 24, and 48 h, the consumption of sufentanil at postoperative 3, 6, 12, 24, and 48 h, and the incidence of major adverse reactions such as shivering, nausea and vomiting, drowsiness and dizziness, and skin itching after surgery were recorded. The mechanical pain threshold of the inner forearm and incision side was tested using an electronic Von Frey stimulator before surgery and 24 h after surgery. Results Compared with groups S, NR, and NPR, group R showed increases in NRS scores at postoperative 1, 3, 6, 12, and 24 h (P<0.05), increases in the cumulative consumption of sufentanil at postoperative 3, 6, 12, 24, and 48 h (P<0.05), and decreases in mechanical pain threshold at the incision site and inner forearm at postoperative 24 h (P<0.05). The mechanical pain threshold of group NR was lower than that of group NPR (P<0.05). There was no statistical difference in the incidence of shivering, nausea and vomiting, drowsiness and dizziness, and skin itching among the four groups (P>0.05). Conclusions The combined use of nalbuphine and parecoxib can effectively prevent RIH after surgery.