Objective To investigate the efficacy and safety of picosecond alexandrite laser therapy in patients with nevus fuscocaeruleus zygomaticus. Methods A total of 82 patients with nevus fuscocaeruleus zygomaticus were selected from the Department of Dermatology, Datong Third People's Hospital from January 2019 to January 2020. According to the sampling method, they were divided into the control group and the study group, with 41 cases in each group. The control group was treated with M22 intense pulsed laser therapy, and the study group was treated with picosecond alexandrite laser therapy. The disease control, clinical indicators, nursing satisfaction and incidence of adverse reactions were compared between the two groups after treatment. Results The effective rate of disease control in the study group was higher than that in the control group, and the duration of scab formation, VAS score and pigmentation time after inflammation were lower than those in the control group. The incidence of adverse reactions after 1 year of treatment was lower than that in the control group, and the treatment satisfaction was higher than that in the control group (P＜0.05)Conclusion After picosecond alexandrite laser treatment, the effective rate of clinical condition control of patients with nevus fuscocaeruleus zygomaticus is higher, which is helpful to reduce the incidence of adverse reactions and improve the satisfaction of treatment. It is worthy of clinical application.