A selective and sensitive fluorometric assay was developed for specific determination of curcumin (Cur) based on fluorescence resonance energy transfer (FRET) between molybdenum disulfide quantum dots (MoS QDs) and Cur. The MoS QDs were prepared via a one-step hydrothermal protocol using sodium molybdate dihydrate, L-cysteine (Cys) as precursors, and sodium cholate (SC) as a modification agent. The as-prepared MoS QDs possessed maximum fluorescence emission at 460 nm with a 20% of fluorescence quantum yield (FQY). It was found that the fluorescence of MoS QDs could be quantitatively quenched by Cur through FRET mechanism. Therefore, Cur could be detected in the range of 0.1-20 µg mL with a detection limit of 5 ng mL. Additionally, the developed MoS QDs based fluorescent assay has been successfully applied for real food sample analysis with satisfactory results.