Objective To explore the application of autologous nanofat transplantation in facial rejuvenation and its inffuence on volume retention. Methods A total of 80 patients undergoing facial rejuvenation treatment admitted to the Department of Burn, Plastic and Aesthetic Surgery, Nanjing Drum Tower Hospital Group Suqian Hospital from January 2020 to January 2024 were selected, and they were divided into the control group and the observation group by the random number table method, with 40 patients in each group. The control group was treated with conventional autologous fat transplantation, and the observation group was treated with autologous nanofat transplantation. The aesthetic effect, volume retention, satisfaction and adverse reactions were compared between the two groups. Results After treatment, the facial fullness scores and skin texture scores of the two groups were higher than those before treatment, and the facial fullness score and skin texture score of the observation group were higher than those of the control group, and the differences were statistically signiffcant (P<0.05). The good volume retention rate of the observation group (75.00%) was higher than that of the control group (55.00%), and the difference was statistically signiffcant (P<0.05). The satisfaction score of the observation group was higher than that of the control group, and the difference was statistically signiffcant (P<0.05). The incidence of adverse reactions in the observation group (12.50%) was lower than that in the control group (40.00%), and the difference was statistically signiffcant (P<0.05). Conclusion Autologous nanofat transplantation for facial rejuvenation can achieve good aesthetic improvement effect, improve the stability of volume retention and patient satisfaction, and effectively reduce the incidence of adverse reactions, which is worthy of clinical application.