In the present study, we found that the expressions of OPN, FGF1 and IGFBP7 were upregulated in keloid-derived stem-like cells in a HH-GLI1 pathway-dependent manner, and the characteristic of keloid, collagen bundle formation, and the expression of inflammatory cytokine IL-6 and fibrosis-inducing factor CTGF was suppressed by the HH signal inhibitor in human keloid tissues. This evidence concerns the gene SPP1 and keloid.