Epidermal growth factor (EGF)-like family members mediate a wide range of biological activities including cell proliferation and migration. Increasing evidence indicated that EGF plays an important role in the process of wound healing by stimulating fibroblast motility. The aim of this study was to see whether EGF-like domain 7 (EGFL7)-overexpressing epidermal stem cells (EGFL7-ESCs) would promote fibroblast proliferation and migration. We found that mRNA and protein levels of EGFL7 expression were significantly increased in EGFL7-ESCs. The protein expression of EGFL7 was significantly elevated in conditioned media (CM) of EGFL7-ESCs compared to ESCs CM or vector-ESCs CM. The cell count and cell viability of EGFL7-ESCs CM-treated fibroblasts were also significantly increased compared to control. In addition, EGFL7-ESCs CM-treated fibroblasts showed elevated migration compared with control. Moreover, the expressions of β1-integrin, β-tubulin, β-actin, and Vimentin were increased, while that of E-cadherin was decreased in EGFL7-ESCs CM-treated fibroblasts. These results indicate that EGFL7-ESCs contribute towards promoting fibroblast migration through enhancing cell adhesion, strengthening cytoskeleton, and reducing intercellular aggregation. These findings suggest that the stimulating effect of EGFL7-ESCs on fibroblast proliferation and migration may provide a useful strategy for wound healing.