Objective To analyze the clinical efficacy of microneedle combined with topical application of supramolecular salicylic acid in the treatment of acne and its effect on the quality of life. Methods A total of 80 patients with acne admitted to our hospital from April 2024 to March 2025 were selected as the research subjects. According to the random number table method, they were divided into the control group and the observation group, with 40 patients in each group. The control group was treated with topical application of supramolecular salicylic acid, and the observation group was treated with microneedle combined with topical application of supramolecular salicylic acid. The clinical symptom scores, clinical efficacy, negative emotion scores and quality of life were compared between the two groups. Results The clinical symptom scores of the observation group after treatment were lower than those of the control group (P <0.05). The total effective rate of treatment in the observation group was 97.50%, which was higher than 80.00% in the control group (P <0.05). The scores of anxiety and depression in the observation group after treatment were (40.35±5.13)scores and (43.13±6.03)scores, respectively, which were lower than (46.35±5.57)scores and (49.76±6.58)scores in the control group (P <0.05). The scores of quality of life in the observation group after treatment were higher than those in the control group (P <0.05). Conclusion Microneedle combined with topical application of supramolecular salicylic acid can effectively promote the regression of acne, improve the quality of life of patients, alleviate negative emotions, and has a good overall treatment effect, which is worthy of clinical application.