The bottom-up synthesis of graphene quantum dots (GQDs) using solvothermal methods has attracted considerable attention because of their fewer defects and controllable size/morphology. However, the influence of organic solvents on the preparation of GQDs is still unknown. Herein, a systematic study on the carbonization of organic solvents toward GQDs is reported. The results show that organic solvents with the double bond or benzene ring or double hydrophilic groups could be directly decomposed into GQDs without the addition of catalysts or molecular precursors. The as-synthesized GQDs demonstrate ultra-small size distribution, high stability, tunable excitation wavelength and upconverted fluorescence. Both hematological and histopathological analyses show that the as-synthesized GQDs demonstrate a very good safety profile and excellent biocompatibility. The versatility of this synthesis strategy offers easy control of the surface group, composition, and optical properties of GQDs at the molecular level.