Chronic stress is a common cause of hair loss, involving inflammatory responses and changes in cellular signaling pathways. This study explores the mechanism of action of the SDF-1/CXCR4 signaling axis in chronic stress-induced hair loss. The research indicates that SDF-1 promotes hair follicle growth through the PI3K/Akt and JAK/STAT signaling pathways. Transcriptome sequencing analysis was conducted to identify differentially expressed genes in the skin of normal and stressed mice, with key genes SDF-1/CXCR4 selected through machine learning and a protein-protein interaction network established. A chronic stress mouse model was created, with injections of SDF-1 and AMD3100 administered to observe hair growth, weight changes, and behavioral alterations and validate hair follicle activity. Skin SDF-1 concentrations were measured, differentially expressed genes were screened, and pathways were enriched. Activation of the PI3K/Akt and JAK/STAT signaling pathways was assessed, and siRNA technology was used in vitro to inhibit the expression of SDF-1 or CXCR4. SDF-1 promoted hair follicle activity, with the combined injection of SDF-1 and AMD3100 weakening this effect. The activation of the PI3K/Akt and JAK/STAT signaling pathways was observed in the SDF-1 injection group, confirmed by Western blot and immunofluorescence. Silencing SDF-1 through siRNA-mediated inhibition reduced cell proliferation and migration abilities. SDF-1 promotes hair growth in chronic stress mice by activating the PI3K/Akt and JAK/STAT pathways, an effect reversible by AMD3100. The SDF-1/CXCR4 axis may serve as a potential therapeutic target for stress-induced hair loss.