Objective: To evaluate the effect of low-dose s-ketamine on cough response during extubation period in patients undergoing suspension laryngoscopic surgery. Methods: From November 2023 to January 2024, 66 adult patients (41 males and 25 females) scheduled for suspension laryngoscopic surgery in Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled, with age of (49.6±11.1) years and American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ. The patients were divided into two groups using a random number table method: treatment group (n=33) and control group (n=33). Patients in the treatment group received 0.25 mg/kg s-ketamine intravenously after induction, and the control group received the same volume of normal saline. The main outcomes included the incidence of cough response and moderate to severe cough response during extubation. The secondary outcomes included heart rate and mean arterial pressure (MAP) at the time of entering the operation room (T0), before intubation (T1), 1 min after intubation (T2), 1 min after suspending laryngoscope (T3), 5 min after suspending laryngoscope (T4), at the end of surgery (T5), and immediately after intubation (T6). Extubation time, the modified Aldrete scores on entering and exiting post-anesthesia care unit (PACU), length of stay in PACU, the numerical rating scale (NRS) scores on exiting PACU and 6 h after surgery and adverse events were also recorded. Results: There were no significant differences in age, gender, ASA grade, body mass index and operation time between the two groups (P>0.05). The incidence of cough response and moderate to severe cough response in the treatment group was 39.4% (13/33) and 12.1% (4/33), respectively. They were significantly lower than those in the control group [66.7% (22/33), 36.4% (12/33)] (all P<0.05). There was no significant difference in the changes of heart rate and MAP between the two groups at any time point (P>0.05). There were no significant differences in extubation time, the modified Aldrete scores on entering and exiting PACU, length of stay in PACU and NRS scores on exiting PACU and 6 h after surgery between the two groups (all P>0.05). No adverse events such as increased secretions, laryngospasm, agitation, nightmare, hallucination, blurred vision and headache were observed in either group. Conclusion: Infusion of low-dose s-ketamine can effectively alleviate cough response in patients undergoing suspension laryngoscopic surgery during extubation period and has no effect on intraoperative hemodynamics, postoperative recovery, or adverse events.