To demonstrate NOX4 function as an indispensable part of TGF-β1 downregulation-induced cancer cell death in A375 cells, both NOX4 siRNA and GKT137831 (ApexBio, Houston, TX, USA) as a NOX4 inhibitor were used to determine whether its inhibition could reverse TGF-β1 downregulation-induced ROS generation/ER stress and subsequent cancer cell death. Here, TGFB1 is linked to cancer.