Objective To investigate the effect of propofol combined with remifentanil anesthesia on postoperative rehabilitation in facial autologous fat transplantation. Methods A total of 121 patients with facial depression admitted to Department of Plastic Surgery, Foshan Mylike Medical Cosmetic Hospital from December 2020 to August 2021 were retrospectively analyzed. All patients underwent facial autologous fat transplantation. According to the different use of anesthetic drugs, they were divided into conventional group (n=59) and combined group (n=62). The conventional group was given propofol anesthesia, and the combined group was given propofol combined with remifentanil anesthesia. The sedation score (Ramsay) 10 min after anesthesia was compared between the two groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and arterial pressure (MAP) were observed before anesthesia and 10 and 30 min after anesthesia. The recovery time and adverse reactions were recorded. Results Ramsay score at 10 min after anesthesia in the combined group was higher than that in the conventional group (P＜0.05). SBP, DBP, HR and MAP at 10 and 30 min after anesthesia in the combined group were lower than those in the conventional group (P＜0.05). The recovery time in the combined group was shorter than that in the conventional group (P＜0.05). The incidence of adverse reactions in the combined group was 3.23%, which was lower than 16.95% in the conventional group (P＜0.05). Conclusion The application of propofol combined with remifentanil anesthesia in patients with facial depression undergoing facial autologous fat transplantation can obtain ideal anesthetic effect, reduce the influence of anesthetic drugs on vital signs, wake up earlier, and have lower risk of adverse reactions, which is helpful for postoperative rehabilitation.