Objective To analyze the effect of platelet-rich plasma combined with autologous fat facial fflling on aesthetic effect in patients undergoing facial rejuvenation. Methods A total of 98 patients undergoing facial rejuvenation admitted to our hospital from June 2021 to June 2025 were selected, and they were divided into the reference group and the study group by the random number table method, with 49 patients in each group. The reference group was treated with autologous fat facial fflling, and the study group was treated with platelet-rich plasma combined with autologous fat facial fflling. The facial skin texture improvement effect, quality of life, aesthetic effect and complications were compared between the two groups. Results The facial skin texture improvement effects of the study group at 1 week after treatment were all better than those of the reference group (P<0.05). The scores of quality of life in the study group at 1 week after treatment were all higher than those in the reference group (P<0.05). The scores of aesthetic effect in the study group at 1 week after treatment were all higher than those in the reference group (P<0.05). There was no statistically signiffcant difference in the incidence of complications between the two groups (P>0.05). Conclusion The application of platelet-rich plasma combined with autologous fat facial fflling in facial rejuvenation can effectively improve facial skin texture, enhance patients' quality of life and aesthetic effect, with high safety.