Objective: To investigate the effects of preemptive analgesia with different doses of hydromorphone on postoperative pain and stress response in patients undergoing radical thyroidectomy. Methods: 92 patients who were to receive radical thyroidectomy in our hospital from January 2022 to January 2024 were selected as the study objects. According to random number table method, 92 patients were randomly divided into high dose group and low dose group, with 46 cases in each group. Low dose group was treated with preemptive analgesia of low dose (0.05?mg/kg) hydromorphone. High dose group was treated with preemptive analgesia of high dose (0.10?mg/kg) hydromorphone. Pain degree [visual analogue score (VAS)], narcotic drug use (time of first request for analgesia, supplemental dose in the analgesic pump and total analgesic drug dosage), blood pressure (systolic and diastolic blood pressure), heart rate and adverse reactions were analyzed and compared between the two groups. Results: The VAS scores of high-dose group at 1, 4, 8 and 24 hours after operation were significantly lower than those of low-dose group (P<0.05). The time of first postoperative analgesia request in the high-dose group was significantly delayed compared with that in the low-dose group (P<0.05), and the analgesic pump supplemental dose and total analgesic drug dosage in the high-dose group were significantly lower than those in the low-dose group (P<0.05). The heart rate, systolic blood pressure and diastolic blood pressure in the high-dose group were significantly lower than those in the low-dose group before surgery, at the end of induction and 1 hour after surgery (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Prophylactic preanalgesia with high dose hydromorphone can improve the analgesic effect and hemodynamic stability of patients after radical thyroidectomy without increasing the risk of adverse reactions.