Under the stimulation of the acidic TME of PC3 prostate cancer cells, biogenic Se nanoparticles at a concentration of 2 μg/mL enabled excessive cellular ROS generation through a Fenton-like reaction, which activated tumor necrotic factor (TNF) and interferon regulatory factor 1 (IRF1)-associated necroptosis. Here, IRF1 is linked to prostate carcinoma.