In this study, we report that IVM, a generic drug approved by FDB, has antibacterial and anti-melanoma activities We further identified the precise molecular target of GSDMD for IVM The current research results show that IVM inhibits the formation of GSDD dependent pores and the thermal swelling of cells, which significantly reduces the formation of reticular structures induced by CTSB, leading to melanoma metastasis. Here, CTSB is linked to melanoma.