Water stable fluorescent ZnO quantum dots (QDs) have been synthesized by wet chemical route in presence of hydrophilic capping agent polyethyleneimine (PEI) as stabilizing agent. The binding interaction of prepared ZnO QDs is studied with bovine serum albumin (BSA) protein. X-ray diffraction measurement reveals hexagonal wurtzite structure of as synthesized ZnO QDs with an average size 4-6 nm, determined using Scherer’s equation and confirmed by transmission electron microscopy (TEM). The ZnO/PEI QDs exhibit strong yellow-green emission centered at 555 nm (2.23 eV). The interaction between BSA and ZnO/PEI QDs has been studied by using spectroscopic and calorimetric methods. Static mode of tryptophan quenching in BSA by ZnO/PEI QDs indicates that a ground state complex formation is taking place between ZnO/PEI and BSA, where, the week interactions (hydrogen bonding and hydrophobic interaction) are contributing towards the stability of the complex.