Quantum dots (QDs) as new fluorescent nanomaterial, have shown potential application for in vivo imaging technology in the past decades, whereas the toxicity of QDs hinders the development of this technology for in vivo application. Here, the authors report a facile, rapid and reproducible route to synthesise protein conjugated CdSe QDs by microwave irradiation. Ribonuclease A protein could serve as a bio-molecular template in the formation of CdSe clusters, and it endows the CdSe QDs with high stability and low bio-toxicity in aqueous medium. The final products were characterised by UV–vis absorption, photoluminescence spectra, X-ray powder diffraction and high-resolution transmission electron microscopy. Furthermore, MTT assay has shown that it has high biocompatibility and low toxicity in vitro.