The design, synthesis, photophysical properties and practical application of fluorescent silicon nanoparticles (SiNPs) of a quantum-size (∼3 nm) have been studied. 3-Aminopropyltrimethoxysilane (APTMS) and 3-aminopropyltriethoxysilane (APTES) were employed as sources. The newly developed nanoparticles show excellent water solubility and luminescent features. Herein we report a novel chemical approach for selective tetracycline (TC) recognition and a new type of targetable fluorescent sensor has been prepared. The blue emission, peaking at 440 nm, was dramatically quenched in the presence of TCs. Moreover, we utilized this probe in a milk sample study for the determination of TCs, demonstrating its advantages of simplicity and practicality.