A multifunctional nanodrug (Tf-DHA-ASO-MnO2) based on manganese dioxide nanosheets was constructed by triple-dressing with transferrin, dihydroartemisinin, and antisense oligonucleotide sequences. Tf-DHA-ASO-MnO2 shows an effective targeted cancer therapy ability through the ferroptosis caused by the production of excessive lipid peroxides resulting from the combined effect of glutathione exhaustion, reactive oxygen species generation and down-regulation of glutathione peroxidase 4.