Objective To analyze the application effect of propofol combined with dexmedetomidine in cosmetic surgery. Methods A total of 80 patients who underwent cosmetic surgery in our hospital from January 2020 to December 2022 were randomly divided into control group and observation group, with 40 cases in each group. The control group was anesthetized with propofol combined with sufentanil, and the observation group was anesthetized with propofol combined with dexmedetomidine. The incidence of adverse reactions, hemodynamic indexes [heart rate (HR), mean arterial pressure (MAP)], stress response indexes [(cortisol (Cor), epinephrine (NE)] and related pain mediators [serum substance P (SP), 5-hydroxytryptamine (5-HT), prostaglandin E2 (PGE2)] were compared between the two groups. Results The incidence of adverse reactions in the observation group was 7.50%, which was lower than 25.50% in the control group (P