Here, we demonstrate that graphene oxide (GO) can act as a structure-directing agent for the formation of PtPd alloy concave nanocubes enclosed by high index facets. In the presence of GO, PtPd alloy concave nanocubes could be easily tailored by a simple hydrothermal reaction. In sharp contrast, only cubic PtPd alloy nanocrystals were obtained in the absence of GO. Moreover, compared to the unsupported PtPd nanocubes, the composition ratio of Pt to Pd changed significantly from 1 : 1 to 3 : 1. Due to the exposed high-index facets and the strong interaction between catalysts and graphene support, the as-synthesized PtPd concave nanocubes exhibited enhanced electrocatalytic activity and high durability toward methanol oxidation. The present work highlights the unique role of GO in the formation of metal nanocrystals as not only a catalyst support but also a structure- and/or morphology-directing agent, due to the presence of various functional groups on GO sheets. The present GO-assisted approach provides a new avenue to the synthesis of nanocrystals with high-index facets and initiates new opportunities for the exploration of high-performance graphene-based nanocatalysts.