Objective To explore the effect of photorejuvenation combined with supramolecular salicylic acid in the treatment of acne vulgaris and its effect on skin lesion score. Methods A total of 62 patients with acne admitted to the Department of Dermatology, Fuyang No.9 Hospital from April 2022 to April 2023 were selected as the research objects. They were divided into control group and observation group by random number table method, with 31 patients in each group. The control group was treated with photorejuvenation, and the observation group was treated with supramolecular salicylic acid on the basis of the control group. The clinical efficacy, skin lesions, acne severity, aesthetics and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 96.77%, which was higher than 83.87% in the control group (P <0.05). After treatment, the skin lesion score and skin lesion area in the observation group were lower than those in the control group (P <0.05). After treatment, the GAGS score of the observation group was lower than that of the control group (P <0.05). The aesthetic score of the observation group after treatment was higher than that of the control group (P <0.05). The incidence of adverse reactions in the observation group was 6.45%, which was lower than 9.68% in the control group, but the difference was not statistically significant (P >0.05). Conclusion Photorejuvenation combined with supramolecular salicylic acid is effective in the treatment of acne vulgaris, which can improve the total effective rate of treatment, improve skin lesions, reduce GAGS score, reduce skin lesion area, and will not increase the incidence of adverse reactions. It is worthy of clinical application.