A kind of nanoparticle is developed for highly efficient chemodynamic therapy that only relies on the endogenous H2O2 of cancer cells. For this nanoparticle, high-molecular-weight DNA is used as the biocompatible carrier to load abundant Mn2+ ions. Therefore, the resultant Mn-DNA coordination nanoparticles can efficiently deliver and sensitively release Mn2+ in cancer cells, resulting in high toxicity through the Fenton-like reaction.