Objective: To explore the effect of oxycodone hydrochloride combined with dexmedetomidine on the recovery quality and stress response during anesthesia in patients undergoing laparoscopic cholecystectomy (LC). Methods: Ninety patients who had LC in Cangzhou Hospital of Integrated TCM-WM of Hebei from December 2016 to December 2019 were selected and divided into dexmedetomidine group (DEX group), oxycodone hydrochloride group (Q group), dexmedetomidine + oxycodone hydrochloride group (DQ group) by a random number table method, with 30 cases in each group. At the time before anesthesia induction (T0), and immediately (T1), 1 min (T2), 10 min (T3) and 30 minutes (T4) after extubation, the general vital signs of three groups were observed, and plasma cortisol (COR), epinephrine (E), norepinephrine (NE) and blood glucose (GLU) were measured. The spontaneous respiration recovery time, wake-up time, VAS score of each time period after extubation, extubation quality score, and adverse event rate were recorded. Results: The vital signs at each time point of extubation, recovery time of spontaneous respiration, wake-up time, and extubation quality of DQ group were better than those of DEX group and Q group (P<0.05). The incidence of agitation, VAS score at T2 and T3, plasma concentrations of Cor, E, NE and Glu at T1, T3 and T4 in DQ group were significantly lower than those in Q group and DEX group (P<0.05). Conclusion: Oxycodone hydrochloride combined with dexmedetomidine can improve the recovery quality and reduce stress response in patients with LC after anesthesia, and can be safely used in patients with LC. doi: https://doi.org/10.12669/pjms.37.5.3959 How to cite this:Wang G, Wu Q, Liu W, Jing Y. Effect of Oxycodone hydrochloride combined with Dexmedetomidine on quality of recovery and stress response after general anesthesia in patients who had Laparoscopic Cholecystectomy. Pak J Med Sci. 2021;37(5):---------. doi: https://doi.org/10.12669/pjms.37.5.3959 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.