A zinc oxide nanowires (ZnO NWs) forest has been grown by a versatile hydrothermal method on solid supports of very different nature, such as flat crystalline silicon, glass fiber and polymer surface. ZnO NWs shown a characteristic photoluminescence (PL) spectrum that has been used for optical transduction of molecular interactions. In this study, ZnO NWs were chemically modified in order to bind a proper bioprobe for selective protein–protein biorecognition. Techniques such as scanning electron microscopy (SEM), water contact angle (WCA), fluorescence microscopy and Fourier transform infrared (FTIR) spectroscopy were used for characterization of nanostructures bioconjugation, demonstrating that ZnO NWs can be easily and efficiently functionalized. Quantitative and label-free sensing of protein–protein interaction was obtained by monitoring PL emission of ZnO NWs under laser irradiation.