Herein, silica nanoparticles (SiNPs) with blue-fluorescence have been originally synthesized through one facile hydrothermal way, and this kind of SiNPs were water-soluble with the relative quantum yield of around 6%. Meanwhile, N-(triethoxysilylpropyl) urea severed as the silica source, while potassium hydrogen phthalate as the doping reagent. Also, SiNPs exhibited the acceptable stability and excitation-dependent fluorescence property. Moreover, their surfaces of the obtained SiNPs were equipped with multiple functional groups including -Si-O-Si-, -Si-H, -COOH, -NH2 and -OH. Importantly, the fluorescence of SiNPs could be specifically quenched by sulfadiazine sodium (SD-Na), thus achieving a label-free detection of SD-Na, which displayed a wide linear response in the range of 0.8 μM-800 μM with a detection limit of 1.02 μM. Additionally, we explored the mechanism of SiNPs sensing SD-Na on the basis of aggregation-induced quenching. To be specific, the particle size of SiNPs increased from 29.9 nm to 203.7 nm induced by the electrostatic interactions between SiNPs and SD-Na, which was further confirmed by high resolution transmission electron microscopy. Consequently, the proposed strategy here broadened the ways of assaying sulfadiazine sodium.