In this study, we demonstrated that derazantinib presented a pleiotropic effect on KFs, which included reduced viability, inhibited migration and invasion, and the downregulation of the expression of PAI-1, a-SMA, and collagen I. Furthermore, in the xenograft nude model, we also demonstrated that intralesional injection of derazantinib inhibited collagen production and reduced the weight of transplanted keloid tissue. The gene discussed is SERPINE1; the disease is keloid.