Objective To analyze the effect of photorejuvenation combined with glycolic acid therapy on skin lesions in patients with melasma. Methods A total of 80 patients with melasma admitted to Gansu Wuwei Tumour Hospital from July 2021 to July 2024 were selected as the research subjects. According to different treatment methods, they were divided into the control group (40 patients) and the observation group (40 patients). The control group received glycolic acid therapy, and the observation group received photorejuvenation combined with glycolic acid therapy. The skin lesions, skin smoothness, aesthetic appearance and adverse reactions were compared between the two groups. Results After treatment, the transepidermal water loss, skin lesion color score, area score and total score in the observation group were lower than those in the control group, and the stratum corneum hydration was higher than that in the control group (P <0.05). The skin smoothness score in the observation group was higher than that in the control group, and the EI and MI were both lower than those in the control group (P <0.05). The incidence of adverse reactions in the observation group (7.50%) was lower than that in the control group (25.00%) (P <0.05). Conclusion Photorejuvenation combined with glycolic acid therapy has a definite effect in the treatment of melasma. It can effectively improve skin lesions, enhance skin smoothness and aesthetic effect, and reduce the incidence of adverse reactions.