Herein, a simple one-pot method for the synthesis of trimetallic PdRuCo hollow nanocrystals is developed. PdRuCo hollow nanocrystals with different compositions can be obtained through a wet-chemical route, just by using a sacrificial Co nanoparticle template. The prepared nanomaterials have been analyzed by transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy, etc. The prepared PdRuCo nanospheres possess an alloyed nanostructure and with an average diameter of about 49 nm. The prepared nanocrystals show much better catalytic activity for ethylene glycol and glycerol electrooxidation than that of a commercial Pd/C catalyst. The reduced cost and enhanced catalytic activity of the as-prepared Pd-based materials allow them to possess great potential applications in direct fuel cells.