To deal with the complex tumor microenvironment (TME), chemodynamic therapy (CDT) has been developed, which uses nanocatalysts simulating peroxidase to convert high concentration hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (˙OH) in situ and effectively kills tumor cells. Due to the low catalytic activity of traditional nanocatalysts, the present CDT treatment has to be combined with other anti-tumor therapies, which increases the complexity and uncertainty of the treatment. Thus, developing new nanocatalysts with stable and high enzymatic activity is the key point to CDT treatment. Graphene quantum dots (GQDs) are important metal-free catalysts with intrinsic peroxidase-like activity due to their excellent electron transport performance. Here, we prepare a nitrogen-doped GQD (NGOD) nanocatalyst, which displays much higher peroxidase activity than known metal nanocatalysts. The NGQD nanocatalyst is further grafted with RGDS peptide-modified polyethylene glycol (PEG), which guides the nanocatalyst to the tumor area and increases its circulation time in blood. The as-produced RGDS-PEG@NG nanocatalyst displays stable and high peroxidase activity, which achieves the conversion of H2O2 → ˙OH in the TME. Through an in vivo study it has been observed that RGDS-PEG@NGs obviously inhibit tumor growth without combining with other treatment methods and show excellent biocompatibility, which provides a unique idea for the application of GQDs in CDT.