Objective To explore the clinical effect of PRP combined with hUC-MSCs in facial skin rejuvenation and its influence on skin condition and wrinkle severity. Methods A total of 124 patients who underwent facial skin rejuvenation in the Fifth Hospital of Harbin City from January 2025 to January 2026 were retrospectively analyzed. According to different treatment schemes, they were divided into the control group and the experimental group, with 62 patients in each group. The control group was treated with facial introduction of physiological saline, and the experimental group was treated with transdermal facial introduction of PRP combined with hUC-MSCs. The skin condition, wrinkle severity, patient satisfaction and adverse reaction rate were compared between the two groups. Results After treatment, the scores of skin elasticity and moisture in the experimental group were higher than those in the control group, and the scores of oil, spots and facial wrinkles were lower than those in the control group (P <0.05). The patient satisfaction rate of the experimental group was 98.39%, which was higher than 40.32% of the control group (P <0.05). The incidence of adverse reactions in the experimental group was 4.84%, compared with 3.23% in the control group, with no statistically significant difference (P >0.05). Conclusion PRP combined with hUC-MSCs can improve skin condition and reduce wrinkle severity in facial skin rejuvenation, with high patient satisfaction and reliable safety.