Objective To study the effect of microneedle injection of collagen and tranexamic acid on MASI score in patients with melasma. Methods A total of 70 patients with melasma admitted to the Department of Dermatology, Xuzhou Central Hospital Affiliated to Medical School of Southeast University from May 2023 to May 2024 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 35 patients in each group. The control group was treated with microneedle injection of tranexamic acid, and the observation group was treated with microneedle injection of collagen combined with tranexamic acid. The facial image analysis parameters, MASI score and adverse reactions were compared between the two groups. Results Compared with the control group, the improvement degree of facial image analysis parameters in the observation group was better (P <0.05). The MASI score in the observation group after treatment was (5.79±2.68)scores, which was better than (7.97±2.43)scores in the control group (P <0.05). Compared with the incidence of adverse reactions in the control group (25.71%), the incidence of adverse reactions in the observation group (5.71%) was lower (P <0.05). Conclusion For patients with melasma, treatment with microneedle injection of collagen combined with tranexamic acid has an obvious facial improvement effect. It can effectively improve the area and severity of melasma and reduce the incidence of adverse reactions, which is worthy of clinical application.