Objective: To evaluate the efficacy and safety of fractional laser combined with polydeoxyribonucleotide in skin luster, texture, pores, and overall aesthetic effect of the face. Methods: A prospective, single-center, self-controlled study design was used, including 9 subjects seeking treatment for facial skin rejuvenation. The control side received fractional laser treatment on one side of the face for all subjects, and the combined treatment side received intradermal of polydeoxyribonucleotide immediately after fractional laser treatment. The efficacy was comprehensively evaluated by quantification scores via VISIA skin analyzing instrument, doctor"s aesthetic improvement assessment (GAIS), and patient satisfaction survey at pre-treatment, 1 month, 3 months, and 6 months after treatment. Adverse reactions to the treatment were recorded and analyzed. Results: At each time point after treatment, there was an improvement in skin luster, texture, and pore size compared with baseline (P<0.05). The improvement of skin luster (t=15.732,P<0.001), delicate texture(t=14.228, P<0.001), and pore reduction (t=12.954, P<0.001) was better in the combined treatment side than in the laser-only side (P<0.05). The results of GAIS showed that proportion of "marked improvement" and "very marked improvement" in the combined treatment side reached 88.9% at 6 months after surgery, which was higher than that the control side 66.7% (X2=12.857, P=0.002). The overall satisfaction of the subjects with the treatment side was 91.1%. The adverse reactions were mainly temporary erythema and edema, and the combined side did not increase the risk of serious adverse. Conclusion: Fractional laser combined with polydeoxyribonucleotide treatment can synergistically enhance the efficacy, showing better clinical efficacy than laser treatment alone improving skin luster, texture, and pore enlargement of the face, with good safety and high patient satisfaction, it is a comprehensive treatment program for facial skin rejuvenation promoting.