We aimed to evaluate the efficacy of the Intranasal Atomized Dexmedetomidine (IAD)+Intranasal Atomized Butorphanol (IAB) combination therapy on adult burn patients undergoing dressing changes. Herein, 46 adult burn patients were enrolled and randomly divided into two groups: Dexmedetomidine-Butorphanol (DB) and Saline-Butorphanol (SB), treated with atomized dexmedetomidine+butorphanol and saline +butorphanol, respectively. The primary outcomes were the Ramsay Sedation Scale (RSS) and the Visual Analog Scale (VAS) scores. The secondary outcomes were Mean Blood Pressure (MBP), Heart Rate (HR), Respiratory Rate (RR), peripheral blood oxygen saturation (SpO2), total butorphanol consumption, and Adverse Effects (AEs). The two groups were comparable in age, sex, weight, and Total Burn Surface Area (TBSA). During dressing changes, the DB group exhibited significantly lower RSS levels (P<0.05). Besides, the two groups showed no significant differences in VAS scores across all measurement time points. Notably, the DB group exhibited decreased MBP at the beginning of the operation (P<0.0001), 10 min after (P<0.0001), and 20 min after (P=0.0205). HR decreased significantly at the beginning (P=0.0005) and 10 min after (P=0.0088) in the DB group. Furthermore, the two groups showed no significant differences in RR and SpO2 levels. Additionally, the rescue butorphanol dose was lower in the DB group (P<0.001). Finally, dizziness and nausea incidences were significantly lower in the DB group (P<0.05). In conclusion, besides its hemodynamic adverse reactions, the IAD+IAB combination therapy exerted a better sedation effect in adult burn patients than IAB treatment alone.