BACKGROUND: The Yunnan-Guizhou Plateau's high-altitude setting is characterized by intense solar ultraviolet radiation, a significant environmental stressor that frequently leads to skin barrier damage. This damage presents clinically as erythema, itching, and desquamation, underscoring the need for effective reparative interventions. AIMS: The objective of this study was to assess the therapeutic efficacy of a novel treatment protocol that integrates non-crosslinked hyaluronic acid (HA) injection with microneedle application of human epidermal growth factor (hEGF) for the restoration of skin barrier function in regions of high altitude. METHODS: Sixty female subjects exhibiting characteristic signs of skin barrier impairment were randomized into four cohorts: a control group and three experimental groups differentiated by hEGF concentration. The intervention comprised subdermal HA injection coupled with microneedle therapy. The VISIA digital skin analysis system was utilized to quantify skin barrier integrity, with assessments performed by a panel of dermatologists and through patient self-evaluations at baseline and postintervention. RESULTS: A marked reduction in erythema and indices of skin barrier damage was observed in the experimental groups relative to the control. The cohort administered 10 000 IU hEGF exhibited the most pronounced restoration of skin barrier function, indicative of a dose-dependent therapeutic response. The treatment demonstrated favorable tolerability without any reported adverse events. CONCLUSIONS: The conjoint application of non-crosslinked HA and hEGF presents as a potent therapeutic modality for the repair of the skin barrier in high-altitude environments. Our findings indicate that an optimized concentration of hEGF is pivotal for achieving the most efficacious treatment outcomes.