We are presenting a three-dimensional mathematical model and simulation for zinc-oxide nanowire field effect transistor (ZnO NW-FET) biosensor for detecting streptavidin/biotin binding. Implementing previously performed physical vapor deposition (PVD) techniques, ZnO NWs were synthesized with diameters in the range of 50-120 nm and lengths of 2-7.1 μm . Our model is developed by using these dimensions and incorporating a spherical molecule model with uniform charge distribution that is immersed in a solvent with mobile univalent ions as developed in . Applying Poisson-Boltzmann equation for boundary and continuity conditions, expression for the electrostatic potential distribution is obtained. This distribution is used to obtain the gate voltage and develop the I-V curves for ZnO NW-FET when used as a biosensor. In the saturation region, the I-V curves demonstrate that small changes in the gate voltage leads to exponentially larger changes in the drain current and allows for single biomolecule detection.