The interfacial adhesion behaviour of a ZnO nanowire-Si substrate system is investigated using an in situ scanning electron microscope (SEM) mechanical peeling technique. The peel front of a nanowire advances via stick-slip events, and an equilibrium between the driving and resistant force to separation occurs immediately prior to a slip event. The interfacial adhesion energy is one order higher than that predicted theoretically by van der Waals interactions. The enhanced adhesion is primarily attributed to chemical and electrostatic interfacial interactions induced by electron irradiation. This work demonstrates that the operating environment of a nanoscale system could dramatically influence its adhesion behaviour. These findings are expected to have significant implications for interpreting the adhesion behaviour exhibited by a 1D nanostructure-substrate system when applying different testing methodologies, and for the fabrication of future NEMS devices.