Objective: To study the clinical effect of microneedling combined with supramolecular salicylic acid topical application in the treatment of acne and its influence on the quality of life. Methods: Eighty patients with acne admitted to our hospital from April 2024 to March 2025 were selected and grouped according to the random number table method. The control group (n=40) was treated with supramolecular salicylic acid external application therapy, and the observation group (n=40) was treated with microneedling based on the control group. The clinical symptom scores of the two groups before and after treatment were compared. Total effective rate of treatment Negative emotion scores before and after treatment Quality of life scores before and after treatment. Result: After treatment, the clinical symptom score of the observation group was lower than that of the control group (P < 0.05); After the treatment, the total effective rate of treatment in the observation group was higher than that in the control group (P < 0.05). After the treatment, the negative emotion score of the observation group was lower than that of the control group (P < 0.05). After the treatment, the quality of life score of the observation group was higher than that of the control group (P < 0.05). Conclusion: The treatment of acne patients with microneedling combined with supramolecular salicylic acid external application can promote the elimination of acne, improve the quality of life of patients, and improve the mood of patients, with good effects.