AbstractHerein, a one‐step solvothermal strategy to synthesize amphiphilic, highly fluorescent graphene quantum dots (GQDs) as nucleus‐targeted fluorescence probes is reported. The edge‐functionalization of GQDs with N and Cl ligands renders them amphiphilic and positive charged for boosting membrane crossing and histone binding in the nuclei. The fluorescent properties of the GQDs can be markedly enhanced by Cl doping, and thus their fluorescence quantum yield is raised to 30% under optimized Cl doping. The self‐targeted GQDs exhibit multicolor cell imaging capability for visualization of fine architectures of the nucleus such as the nuclear envelope and nucleoli, which can be associated with their distinct surface features like amphiphilicity and high positive charge. These findings serve as a simple nuclear targeting strategy for cancer diagnosis and therapy.