Objective To investigate the effect of 755 honeycomb picosecond laser combined with microneedle introduction of tranexamic acid in the treatment of melasma and its influence on clinical symptoms of patients. Methods A total of 120 patients with melasma admitted to Xinjiang Vcharm Plastic Surgery Hospital from September 2023 to September 2024 were selected as the research subjects. According to the random number table method, they were divided into the control group (n =60) and the observation group (n =60). The control group was treated with 755 honeycomb picosecond laser combined with local microdroplet injection of tranexamic acid, and the observation group was treated with 755 honeycomb picosecond laser combined with microneedle introduction of tranexamic acid. The clinical efficacy, clinical symptoms and quality of life were compared between the two groups. Results The total effective rate of treatment in the observation group (95.00%) was higher than that in the control group (80.00%) (P <0.05). The scores of skin color, lesion area and the total symptom score in the observation group after treatment were lower than those in the control group (P <0.05). The MELASQOL score in the observation group after treatment was lower than that in the control group (P <0.05). Conclusion 755 honeycomb picosecond laser combined with microneedle introduction of tranexamic acid has a good effect in the treatment of melasma, which is beneficial to improve clinical symptoms and enhance the quality of life of patients.