Stacking fault tetrahedron (SFT) is a common type of three-dimensional vacancy clustered defect in irradiated FCC metals and alloys, which has a great influence on the mechanical properties of the materials. Previous researches mostly concentrated on the effect of SFT on the mechanical response of material under quasi-static or constant strain rate loading condition, while very few studies focused on its influence on mechanical properties under the shock loading condition. Spallation is a typical failure mode of ductile metal material under shock loading, and the initial defects in the material have a great influence on the spallation behavior. In this study, molecular dynamics simulation is carried out to investigate the influence of SFT on spallation behavior of irradiated copper single crystal under different shock intensities. Copper single crystal with a perfect structural model is also investigated under the same simulation condition for comparison. The model is divided into two parts: the flyer and the target. The shock wave is generated by moving the flyer at a velocity in a range of 1.0–2.5 km/s along the [111] crystallographic orientation to achieve the desired shock-state particle velocityU_p in a range of 0.5–1.25 km/s. The time evolution of pressure, free surface velocity and corresponding microstructure, are analyzed in detail to illuminate the spallation behavior of the Cu with SFT. It is revealed that the SFT collapses during shock compression and induces the generation of dislocations and stacking faults in the material. Subsequently, spallation happens when the voids nucleate and grow in the region of dislocations and stacking faults. Moreover, the materials show different spallation behaviors at different shock intensities. When U_p ≤ 1.0 km/s, only elastic deformation occurs in perfect single crystal copper under shock compression, but in the copper with SFT, local defects appear and plastic deformation occurs due to the collapse of SFT under shock compression. The influence of SFT on spallation is most pronounced at a medium shock intensity. When U_p = 0.75 km/s, the local defects caused by the collapse of SFT provide a wider nucleation area for the voids and promote the heterogeneous nucleation of the voids, resulting in the decreasing of the spall strength. The void nucleation of single crystal copper with SFT is found to be much later than the perfect one and the rate of spall damage evolution also decreases due to energy dissipation during SFT’s collapse and plastic deformation. When U_p increases to 1.25 km/s, shock compression induces many defected atoms in both samples, so the SFT has little influence on the spall strength and spall damage of the materials.