Objective To explore the effect of fractional laser combined with platelet-rich plasma (PRP) sequential therapy on skin barrier function in patients with facial pigmentation. Methods A total of 100 patients with facial pigmentation treated in the Department of Burn and Plastic Surgery, Miyun District Hospital, Peking University First Hospital from January 2022 to December 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 50 patients in each group. The control group received fractional laser treatment, and the observation group received fractional laser combined with PRP sequential therapy. The clinical efffcacy, facial pigmentation status, skin barrier function and adverse reaction rate were compared between the two groups. Results The total effective rate in the observation group was higher than that in the control group (P<0.05). The percentages of brown spots and ultraviolet spots in the observation group at 3 months after treatment were lower than those in the control group (P<0.05). At 1 month after treatment, the TEWL and erythema index in the observation group were higher than those in the control group, and the stratum corneum hydration was lower than that in the control group (P<0.05). However, the variation ranges of all indicators in the observation group were smaller than those in the control group. At 3 months after treatment, the TEWL and erythema index in the observation group were lower than those in the control group, and the stratum corneum hydration was higher than that in the control group (P<0.05). The incidence of adverse reactions in the observation group was lower than that in the control group (P<0.05). Conclusion Fractional laser combined with PRP sequential therapy is effective in the treatment of facial pigmentation. This protocol can not only improve facial pigmentation, but also effectively promote the repair of skin barrier function, with favorable overall safety.