We report a remarkable phenomenon that electron beam irradiation (EBI) significantly enhances the Young's modulus of zinc tin oxide (ZTO) nanowires (NWs), up to a 40% increase compared with the pristine NWs. In situ uniaxial buckling tests on individual NWs were conducted using a nanomanipulator inside a scanning electron microscope. We propose that EBI results in substantial atomic bond contraction in ZTO NWs, accounting for the observed mechanically stiffening. This argument is supported by our experimental results that EBI also reduces the electrical conductivity of ZTO NWs.