Objective: To analyze the effect of oliceridine and sufentanil on stress response and gastrointestinal motility in patients with laparoscopic total hysterectomy.Methods: The study subjects were 126 patients who underwent laparoscopic total hysterectomy, and were divided into group A and group B according to the different doses administered during anesthesia induction, with 63 cases in each group. During anesthesia induction, group A was given oliceridine, and group B was given sufentanil. The postoperative sedation status (RAMSAY sedation score), postoperative gastrointestinal motility (first exhaust and defecation time, bowel sound recovery time), stress response [serum norepinephrine (NA), adrenocorticotropic hormone (ACTH), cortisol] and occurrence of adverse reactions at 1 d after surgery were compared between the two groups.Results: Group A had shorter postoperative first exhaust time, defecation time and bowel sound recovery time compared to group B (P<0.05). RAMSAY sedation scores in group A at 12 and 24 h after surgery were higher compared to group B (P<0.05). The levels of serum NA, ACTH and cortisol in the two groups of patients were higher at 12 and 24 h after surgery than those before surgery (P<0.05), and the above levels in group A were lower than those in group B (P<0.05). Group A showed a lower total incidence rate of postoperative adverse reactions than group B (3.17% vs. 14.28%, P <0.05).Conclusion: Compared with sufentanil, oliceridine can more effectively relieve the body’s stress level in patients undergoing laparoscopic total hysterectomy, with fast recovery of postoperative gastrointestinal motility, good sedative effect and high safety.