Objective To explore the effect of autologous fat transplantation combined with type A botulinum toxin injection in patients with nasolabial fold depression. Methods A total of 120 patients with nasolabial fold depression admitted to our hospital from August 2020 to August 2023 were selected and divided into study group and control group by random number table method, with 60 patients in each group. The control group was treated with autologous fat transplantation, and the study group was treated with autologous fat transplantation combined with type A botulinum toxin injection. The clinical efficacy, wrinkle severity, facial aesthetic recovery, quality of life, adverse reactions and treatment satisfaction were co mpared between the two groups. Results The total effective rate of treatment in the study group was 96.67%, which was higher than 85.00% in the control group (P <0.05). The WSRS score of the study group was lower than that of the control group at 6 months after treatment (P <0.05). The GAIS score of the study group was higher than that of the control group (P <0.05). The scores of all dimensions of quality of life in the study group were higher than those in the control group at 6 months after treatment (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). The total treatment satisfaction of the study group was 95.00%, which was higher than 76.67% of the control group (P <0.05). Conclusion Autologous fat transplantation combined with type A botulinum toxin injection has a good effect on improving nasolabial fold depression, which can effectively reduce the nasolabial groove wrinkles of patients, promote facial aesthetic recovery, and improve their quality of life. The incidence of adverse reactions after treatment is low, and the treatment satisfaction is high.