To analyze the application effect of autologous fat filling combined with V-face lifting in facial rejuvenation treatment. Methods A total of 68 patients with facial rejuvenation treated in our clinic from February 2022 to August 2023 were selected and divided into observation group and control group according to random drawing method, with 34 patients in each group. The control group was treated with V-face lifting, and the observation group was treated with autologous fat filling combined with V-face lifting. The clinical efficacy, facial morphological parameters and postoperative complications were compared between the two groups. Results The excellent and good rate of the observation group was 91.18%, which was higher than 70.59% of the control group (P <0.05). The mandibular angle, lateral canthus zygomatic point spacing, temporal eyebrow zygomatic point spacing and orbital zygomatic point spacing in the observation group were higher than those in the control group (P <0.05). The incidence of postoperative complications in the observation group was 14.71%, which was lower than 38.24% in the control group (P <0.05). Conclusion In the treatment of facial rejuvenation, autologous fat filling combined with V-face lifting can improve the therapeutic effect, improve facial morphology and reduce the incidence of complications, which is worthy of clinical application.