A new method for silica-coated CaF 2 :Eu 3 + core-shell nanoparticles functionalized with oxalic acid for bio-conjugation to bovine serum albumin (BSA) proteins has been developed. Moreover, CaF 2 :Eu 3+ /SiO 2 core-shell nanoparticles modified with oxalic acid are biocompatible and can be dispersed in water. As an organic functional molecule, oxalic acid is able to react with hydroxyl groups existed on the surface of SiO 2 layer by esterification reaction to form carboxylic acid for further bio-conjugation with BSA. The final products were characterized by means of X-ray diffraction (XRD), transmission electron microscope (TEM), field-emission scanning electron microscopy (FE-SEM), ultraviolet (UV) spectrophotometer, infrared (IR) spectrophotometer and photoluminescence (PL) spectra. XRD result confirmed the phase purity of with pH ranging from 2 to 9. Therefore, these luminescent colloidal nanoparticles can be potentially employed as targeted fluorescent labels in biomedical research applications.