Objective To observe the effect of nalbuphine combined with ketorolac tromethamine pretreatment on acute hyperalgesia after video-assisted thoracic surgery (VATS).Methods 72 patients with stage I or II non-small cell lung cancer undergoing VATS lobectomy under elective general anesthesia in our hospital from September 2020 to September 2021 were randomly divided into control group (group C), nalbuphine group (group N) and nalbuphine combined with ketorolac tromethamine group (group L), with 24 cases in each group. Before anesthesia induction, group L was intravenously injected with nalbuphine + ketorolac tromethamine, group N was intravenously injected with nalbuphine, and group C was injected with the same amount of normal saline. The mechanical pain thresholds of the medial forearm and around the incision were measured by electronic pain meter (Von Frey) before operation, 6 h, 24 h and 48 h after operation. The numerical rating scale (NRS) was evaluated at 30 min, 6 h, 24 h and 48 h after operation. The cumulative consumption of sufentanil and the incidence of adverse reactions within 48 h after operation in 3 groups were compared and analyzed.Results There were statistically significant differences in the mechanical pain thresholds of the medial forearm and around the incision at 6 h, 24 h and 48 h after surgery among the three groups (P < 0.05). There were statistically significant differences in NRS and at 30 min, 6 h and 24 h after operation and sufentanil cumulative consumption within 48 h after operation among the three groups (P < 0.05). The mechanical pain threshold of the medial forearm and the mechanical pain threshold around the incision in group N and group L at 6, 24 and 48 h after surgery were higher than those in group C, and the NRS at 30 min, 6 h and 24 h after operation and the cumulative consumption of sufentanil within 48 h after operation were lower than those in group C (P < 0.05). The mechanical pain threshold around incision at 6, 24 and 48 h after operation in the group L was higher than that in the group N, and the NRS at 30 min, 6 h and 24 h after operation and the cumulative consumption of sufentanil within 48 h after operation were lower than that in the group N (P < 0.05).Conclusion Ketorolac tromethamine combined with nalbuphine pretreatment can prevent and treat acute hyperalgesia after VATS and reduce postoperative pain and analgesic needs.