Skins expose to kinds of risk factors for damage, such as the hormone drugs, skin care products and ultraviolet radiation, which is accompanied by the production of excessive reactive oxygen species (ROS) and eventually leads to hypertrichosis. These skin diseases are not aesthetically pleasing and even cause psychological and spiritual problems such as inferiority, anxiety and irritability. Current therapies are limited and often unsatisfactory, such as pharmacological and physical therapies, which have adverse effects and cause the irreversible destruction of hair follicles. Gold nanoclusters have good biocompatibility and its biosynthesis in vivois responsive to oxidative stress microenvironment (OSM), which could be a safe and effective drug for ROS-induced skin injury. In our study, we demonstrated that zero valence fluorescent gold nanoclusters (FGNCs) were in situbiosynthesized in the plucking-induced damaged skin but not in the normal skin after the administration of gold precursors (+3), while FGNCs inhibited hair follicle regeneration by negatively regulating nuclear transcription factor kappa B (NFκB)-mediated inflammatory response signaling pathway (NFκB/tumor necrosis factor-α(TNF-α) axis). This OSM-responsive in situbiosynthesis method is facile and safe and holds great promise for curing hypertrichosis associated with skin dermatitis and injury.