Nanoindentation experiments were conducted on Zr65Cu15Al10Ni10 bulk metallic glass samples with pre-compression deformation (PCD) under various conditions. By analyzing indentation hardness, residual morphology, pile-up, and serrated flow, the effects of PCD on nanoindentation response were comparatively investigated. Experimental results indicate that 9 kN PCD induced remarkable decrease of indentation hardness, i.e. softening of the material, while for the 18 kN and 25 kN PCD samples, hardness values very close to that of the as cast sample were obtained. Furthermore, PCD also changed the mechanical heterogeneity, i.e., distribution of soft and hard regions in the bulk metallic glass. Residual morphologies and load-displacement curves of the 9 kN and 18 kN PCD samples showed opposite features in aspects of macroscopic shear bands, pile-up width, pile-up height, and serrated flows, suggesting different plastic flows during nanoindentation. To rationalize these phenomena, a competing mechanism between shear bands and compressive residual stress was discussed.