Quasi-continuum method is applied to investigate the anisotropic behavior of nanoscale adhesive contact when a Ni tip indents into and then pulls out of single crystal Cu substrates. For ((1) over bar 10) substrate, the Ni tip exhibits excellent brittle behavior. Interface fracture is mainly characterized by atomic rearrangement since few slip planes are available. For (001) substrate, Shockley partials and deformation twins are both observed during the indentation process. Interface fracture is dominated by atomic slip which leads to the ductile fracture of the interface. As for (111) substrate, the nanocontact leads to significant plastic deformation of the substrate and the piling up of Cu atoms as well as the wetting of the Ni tip. This is because the Ni tip and Cu substrate share the same crystal orientations and the misfit effect between them is less evident. These anisotropic adhesive behaviors illustrate the importance of choosing a proper crystal contact surface to prevent wearing in micro-electro-mechanical systems. Distinctive nanocontact-induced deformation mechanisms and fracture mechanisms are revealed and analyzed. We found that available slip systems should be paid enough attention to for adhesive contact at nanoscale. It is recommended that adhesive contact between the Ni tip and Cu substrate with the same orientations should be avoided in order to reduce wearing. Some of the results found in our work are also validated by similar or related experiments by other researchers. (C) 2014 Elsevier B.V. All rights reserved.