In this study, we demonstrated that GSDMD proteins could be efficiently transported to the cytoplasm of tumor cells, in which the VNP could trigger the activation of cleaved caspase 1 to transform intracellularly delivered GSDMD into pore-forming domain N-terminal GSDMD for binding to the plasma membrane and subsequently triggering pyroptosis in tumor cells. Here, CASP1 is linked to neoplasm.