We previously reported that the induction of autophagic cell death by the small-molecule compound THPN could be an option for melanoma treatment.22,23 Here, we further combined iron with ROS-inducing drugs that can boost the cellular ROS level to activate the Tom20-Bax-caspase-GSDME signaling pathway and ultimately induce the pyroptotic death of melanoma cells. This evidence concerns the gene TOMM20 and melanoma.