It was well demonstrated that the higher ROS gradient in the glioma microenvironment stimulated the release of TBTP‐Au from the NPs, and Au(I) selectively bound with the over‐expressed TrxR and triggered the specific HMOX1‐regulated noncanonical ferroptosis activation of glioma cells, which induced notable tumoral suppression and the extension of the survival time. The gene discussed is HMOX1; the disease is glioma.