This study aimed to investigate the effect of exosomes from adipose-derived mesenchymal stem cells (ADSC-Exos) on the proliferation of human epidermal stem cells (EpSCs) and explore the underlying mechanisms. ADSCs were isolated from human adipose tissue by type Ⅰcollagenase digestion. EpSCs were isolated from human skin tissue by dispase Ⅱ and trypsin digestion. The exosomes were isolated from the supernatant of ADSCs using the ExoQuick-TC reagent. EpSCs proliferation was examined by MTT assay, immunofluorescence staining of Ki67 and BrdU incorporation assay. Cell cycle phase distribution was analyzed by flow cytometry. Cultured human skin tissues were examined for the structure and expression of the markers of cell proliferation and epidermal stem cells by H&E staining and immunohistochemistry, respectively. The results showed that ADSC-Exos promoted EpSCs proliferation in concentration- and time-dependent manners. ADSC-Exos increased the number of cells in S phase, and decreased the number of cells in G1 phase. ADSC-Exos also significantly promoted the proliferation of EpSCs in cultured skin tissue. Mechanistic study showed that the proliferative activity of ADSC-Exos was partially inhibited by β-catenin inhibitor XAV-939 or c-Myc inhibitor 10058-F4. ADSC-Exos upregulated the expressions of β-catenin, c-Myc, cyclins E1, A2 and D1. XAV-939 suppressed ADSC-Exos-induced expressions of β-catenin, c-Myc, cyclins E1, A2 and D1. 10058-F4 inhibited the upregulation of c-Myc and cyclins E1, A2 and D1 by ADSC-Exos. Collectively, these results indicate that ADSC-Exos promote EpSCs proliferation partly through upregulating the expression of β-catenin, c-Myc and cyclins.