【Abstract】Objective To study Application of oxycodone hydrochloride injection combined with dexmedetomidine in laparoscopic cholecystectomy and its effect on thrombin A2, plasma endothelin and analgesic effect. Methods Ninety laparoscopic cholecystectomy patients admitted to our hospital from April 2017 to April 2019 were selected for the study, were randomly divided into the combined group (n=35), the oxycodone group (n=30) and the dexmedetomidine group (n=25). Dexmedetomidine group was given dexmedetomidine, oxycodone group was given oxycodone hydrochloride, and combination group was given oxycodone injection combined with dexmedetomidine. The waking time, extubation time, anal exhaust time, thrombin A2, plasma endothelin, pain score and adverse reactions were compared among the three groups. Results The recovery time, extubation time and anal exhaust time in the combined group were significantly lower than those in the oxycodone group and the dexmedetomidine group (P＜005). At T0 and T1, there was no significant difference in thrombin A2 and plasma endothelin levels among the three groups. At T2, T3 and T4, the levels of thrombin A2 and plasma endothelin in all three groups were significantly increased, and the combined group was lower than the oxycodone group and the dexmedetomidine group, with significant differences (P＜005). At 6h, 12h, 24h and 48h after surgery, pain scores of the combined group were significantly lower than those of the oxycodone group and the dexmedetomidine group, with significant differences (P＜005). The total incidence of adverse reactions in the combined group was 1143%, significantly lower than 3000% and 4000% in the oxycodone group and dexmedetomidine group (P＜005). Conclusion In laparoscopic cholecystectomy, oxycodone hydrochloride injection combined with dexmedetomidine has a significant effect, which can effectively improve the level of thrombin A2, plasma endothelin and pain without increasing adverse reactions.