Nanoindentation of Ni-based single crystal alloy which has a void defect is simulated by the molecular dynamics method. Three models with different voids which have a same radius but different depth (H=1.5 nm, 3.0 nm, 4.5 nm) are contrasted to the perfect model respectively. The influence of a void and misfit dislocation on nanoindentation process are analyzed using center symmetry parameter. Nucleation and growth of dislocation on various indentation depth are researched simultaneously. After relaxation, misfit dislocations occur in all models, which indicates that the void does not affect the generation of misfit dislocation in γ/γ' phase. The indentation load-depth curves show the shallow void (H=1.5 nm) has the greatest influence on nanoindentation. The results demonstrate that the void has two different ways to affect the nanoindentation process. Initially, the void softens the materials when the indentation depth is less than 0.375 nm. However, it will hinder the growth of dislocations because of a kind of surface force, which causes the increase of indentation load while the indentation depth is between 0.375 nm and 0.567 nm. The collapse of a void absorbs the strain energy, so the amount of stacking faults nucleation in γ phase in model with the shallow void is less than which in the perfect model. The indentation load-depth curves show that the indentation load in the H=1.5 nm model is larger than load in the perfect model at 1.263 nm indentation depth. But when the void collapses completely, dislocations tangle around the original location of the void and more stacking faults generate comparing to the perfect model at the same indentation depth h=1.743 nm. So the indentation load declines and becomes smaller than load in perfect model. If the void locates at the interface of γ/γ' phase (H=3.0 nm), it influence the nanoindentation process later than H=1.5 nm model. Dissociation of misfit dislocations is observed when the indentation depth arrives the maximum value 1.748 nm in H=3.0 nm model. Stairs form on the surface of γ phase because of the dissociation of misfit dislocations. There is almost no influence on the nanoindentation of Ni-based single crystal alloy when the void locates in the γ' phase (H=4.5 nm).