In this study, the effect of substrate orientation on the structural quality of Au-catalyzed epitaxial GaAs nanowires grown by a molecular beam epitaxy reactor has been investigated. It was found that the substrate orientations can be used to manipulate the nanowire catalyst composition and the catalyst surface energy and, therefore, to alter the structural quality of GaAs nanowires grown on different substrates. Defect-free wurtzite-structured GaAs nanowires grown on the GaAs (110) substrate have been achieved under our growth conditions.