Abstract： Objective To evaluate the efficacy and safety of low-fluence and large spot-size 1064-nm Q-switched Nd∶YAG laser combined with glutathione hormone (GSH) and vitamin C for the treatment of melasma.Methods This study recruited 12 female melasma patients,with the age averaging (42.3 ± 6.56) years and varying from 32 to 56 years.The whole face with melasma lesions of all the patients were irradiated with 1064-nm Q-switched Nd∶YAG laser (Medlite C6) at fluences of 2.5-3.0 J/cm2 and a spot size of 6 mm for 8 sessions with an interval of 1 week followed by 6 sessions with an interval of 1 month.The patients also received 3 courses of 14-consecutive-day treatment with intravenous GSH 0.9 g and vitamin C 2 g once a day at a 3-month interval.Photographs were taken and melasma area and severity index (MASI) was calculated for the patients before and after the treatment.Results Of the 12 patients,1 was cured,5 markedly improved,6 improved,and all showed clinical response.The average MASI decreased from 13.8 ± 4.3 before treatment to 7.1 ± 2.4 after treatment (P＜ 0.05).Follicular orifices constricted and skin became smoother with no hypopigmentation or hyperpigmentation observed in the patients after the treatment.Conclusion The lowfluence,large spot-size,1064-nm Q-switched Nd ∶ YAG laser combined with GSH and vitamin C is a safe and effective treatment modality for melasma with no requirement for downtime.