In this paper, the plastic deformation mechanism of pre-void Ni/Ni3Al interface alloy under tensile load dependent on the size of pre-existing void in Ni/Ni3Al interface is investigated by using molecular dynamics simulations with Embedded Atom Method (EAM) potential. It is interesting that for the special case of infinitely long cylindrical voids, it is found that the pre-void Ni/Ni3Al interface structures with relatively smaller radius produce higher yield stresses than the void-free sample, as the smaller voids in interface help to disperse the local energy induced by the interface misfit in elastic tension. The competition between the initial edge dislocation formed from lattice misfit and Shockley partial nucleated from the pre-void contributes to triggering the varying dislocation nucleation and plastic deformation patterns. And it is found that the propagations of the slip bands emitted from Stair-rod dislocation and stacking faults generated from Shockley partial are the main plastic deformation mechanism. Moreover, obvious temperature effects on the stress-strain curves and the Young’s modulus are found in the Ni/Ni3Al interface alloy with a constant pre-void radius.