We previously reported that graphene oxide could enhance nuclease activity of copper complex containing aromatic ligands, thus exhibit the potential for applications in anticancer therapy. However, the functional mechanism of graphene oxide is not well understood. In this work, using graphene quantum dots (GQDs), which have smaller lateral size, better biocompatibility, and a conjugate state higher than that of graphene oxide, we investigated systematically the mechanism of GQDs in enhancing nuclease activity of copper complexes. Through a variety of spectroscopic methods, we found that GQDs promote the reduction of copper ions and accelerate their reaction with O 2, forming superoxide anions and copper-centered radicals. These active species then oxidize DNA molecules. The improvement in the reduction of copper complexes can be attributed to the coordination of the GQDs to the copper center of the complex, leading to an efficient electron-transfer from the electron-rich GQDs to the copper complexes. The fundamental understanding of the role of the GQDs in DNA cleavage by the transition complexes is promising for the discovery of anticancer therapeutics. More importantly, unique and rich three-dimensional structures of metal complexes also make it possible to prepare highly active DNA cleavage reagents with a high selectivity for DNA sequences and structures.