The present study reports the surface functionalization of ZnO nanoparticles with functionalized bovine serum albumin (BSA) as a biocompatible system. Sol gel method was adopted for the synthesis of zinc oxide nanoparticles (ZnO NPs). BSA was functionalized with 2-oxo-2H-chromene-3-carboxylic acid (3-CCA) by the DCC (Dicyclohexyl carbodiimide) coupling method. The presence of hydroxyl functional groups in the biopolymer makes it easier to get coupled with carboxylic acid group of the dye. Finally, the ZnO NPs are incorporated into the biomacromolecular system, BSA, which was functionally modified. The various characterizations done for the surface functionalized ZnO NPs are ultraviolet (UV)/visible, Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The antimicrobial resistance of the surface functionalized ZnO NP product were also investigated. The present study also demonstrates the cytotoxicity of this system against Dalton's lymphoma ascites (DLA) cell lines in vitro.