Objective: To investigate the clinical efficacy of Q-switched laser combined with nano-microneedle transdermal delivery of tranexamic acid in the treatment of melasma and analyze its impact on the Melasma Area and Severity Index (MASI) score. Methods: A prospective study was conducted on 106 eligible subjects from the Department of Dermatology at Qinghe County Central Hospital in Xingtai from June 2024 to June 2025. The participants were randomly divided into two groups: the control group (n=53, treated with Q-switched laser alone) and the observation group (n=53, treated with Q-switched laser combined with nano-microneedle transdermal delivery of tranexamic acid). The clinical efficacy, MASI scores before and after treatment, skin condition, and incidence of adverse reactions were compared between the two groups. Results: In terms of efficacy evaluation, the total effective rate in the observation group was significantly higher than that in the control group (P<0.05). The post-treatment MASI score in the observation group was significantly lower, and the improvement in skin condition as assessed by VISIA skin analysis was also more pronounced (both P<0.05). Regarding safety, the incidence of adverse reactions was comparable between the two groups, with no significant difference (P>0.05). Conclusion: Q-switched laser combined with nano-microneedle transdermal delivery of tranexamic acid significantly enhances clinical efficacy in melasma treatment, effectively reduces the MASI score, improves skin pigmentation and vascular abnormalities, and demonstrates good safety.