Abstract: Objective To explore the appropriate effect-site concentration (Ce) of propofol target-controlled infusion (TCI) combined with fentanyl for sedation during fiber-optic bronchoscopy (FOB)-assisted nasotracheal intubation. Methods One hundred and twelve patients undergoing general anesthesia with American Society of Anesthesiologists (ASA) gradeⅠ-Ⅱ for oral cancer surgery admitted to Chinese PLA General Hospital from March 2015 to July 2015 were enrolled in this study. There were 55 males and 57 females with average age of (43.9±12.7) years and body mass index of (24.0±4.0) kg/m², and they were randomly assigned into midazolam group (group M, n=52) and propofol group (group P, n=60). All patients received fentanyl (1.5 µg/kg) after entering the operating room. Patients in group M were injected with midazolam (0.02 mg/kg), and patients in group P were infused propofol TCI at an initial plasma concentration (Cp) of 1.2 µg/ml. Doses of midazolam and Ces of propofol were adjusted according to bispectral index (BIS). 2.5 ml of 2% tetracaine was injected into tracheal through cricothyroid membrane, naso-pharyngeal membrane was infiltrated with 2 ml of 1% tetracaine for topical anesthesia in both groups until BIS value fell to 85. FOB was loaded when BIS value was between 70 and 80. Tracheal tube was placed once FOB passed the glottis, patients in both groups were administrated propofol (1 mg/kg) at the same time. General anesthesia was commenced after nasotracheal tube was secured. Intraoperative and postoperative events were recorded. Propofol Ces at the time of cricothyroid membrane puncture and FOB placed were recorded, respectively. Results There were no significant differences between two groups in the degree of difficult intubation, pain memory, incidence of cough or aspiration and tracheal intubation time. Compared with group M, airway obstruction score and postoperative sore throat score decreased significantly in group P (P＜0.05), while comfort degree of patients increased significantly in group P (P＜0.05). The mean Ces of propofol at the time of cricothyroid membrane puncture and FOB placed was (0.7±0.2) µg/ml and (1.1±0.3) µg/ml, respectively. Conclusion Combined with fentanyl (1.5 µg/kg), the propofol mean Ce (0.7±0.2) µg/ml required for cricothyroid membrane puncture and mean Ce (1.1±0.3) µg/ml required for fibreoptic endoscopy are safe and feasible when it is used for supplement of topical anesthesia for FOB-assisted nasotracheal intubation, and it is superior to midazolam, but additional propofol (1 mg/kg) needs to be injected when nasotracheal tube is placed.