In the present paper, a dislocation dipole model is employed to simulate the nucleation of microvoids at the interface between a thin film and a substrate. In this model, the accumulation of dislocation dipoles plays a major role in the formation of a microvoid. The total free energy of the system increases with the fatigue cycle number due to the increase in elastic strain energy. It is shown that there exists a critical fatigue cycle number beyond which the initial state of dislocation dipole accumulation becomes energetically unstable, and the energy of this state will be released by the formation of a microvoid at the interface. The study can provide not only the S-N curves for the initiation but also their dependence on material parameters such as the thickness of the film, the grain size of the substrate, the shear moduli ratio, etc. The coalescence of those microvoids is expected to be one of the mechanisms of delamination of the thin film from its substrate.