Based on the quenching of the fluorescence intensity of thioglycolic acid (TGA)-capped core-shell CdTe/ZnS nanoparticles (NPs) by vanillin, a novel, simple and rapid method for the determination of vanillin was proposed. In aqueous medium, the functionalized core-shell CdTe/ZnS NPs were successfully synthesized with TGA as the capping ligand. TGA-capped core-shell CdTe/ZnS NPs were characterized by using X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Factors affecting the vanillin detection were investigated, and the optimum conditions were also determined. Under the optimum conditions, the relative fluorescence intensity of CdTe/ZnS NPs was linearly proportional to vanillin over a concentration range from 9.4 × 10(-7) to 5.2 × 10(-4) M with a correlation coefficient of 0.998 and a detection limit of 2.6 × 10(-7) M. The proposed method was also employed to detect trace vanillin in cookies with satisfactory results.