Strong second-order nonlinear effect of ZnO nanowires on a silicon wafer are demonstrated by using the hyper-Rayleigh scattering (HRS) measurement. The large nonlinear effect can be attributed to the following two factors: (1) the large total dipole moment caused by high surface defect density and electrostatic potential gradient, (2) coherent effect due to high crystal quality of single nanowire. Moreover, the second-order nonlinear effect is found to become weaker when the chip is put into organic solvent due to modification of surface defect caused by organic molecules. The variation of second-order signal in the solvent indicated the potential applications of ZnO nanowires as a sensor-on-chip (SoC).