Fuel cells are believed as promising power sources with many advantages including their high efficiency and environment-friendliness. Proton exchange membrane fuel cells (PEMFCs), of which usage can be expected as power sources as automobiles and so on, have yet several problems to resolve for the commercialization. Among them, the high price due to the scarcity of Pt, which is used as anode and cathode catalysts, is one of the most serious issues. Pd is a natural choice to replace Pt because the hydrogen oxidation reaction (HOR) activity of Pd is the next to that of Pt, and Pd is at least fifty times more abundant on earth than Pt. Pd is a more attractive substitute for Pt because of its higher intrinsic CO tolerance than Pt, especially as HOR catalysts for PEMFC where the tolerance of CO, a major impurity of hydrogen fuel, is crucial. Although Pd has comparable HOR activity to Pt, the exclusive use of Pd as anode catalysts of PEMFC has not been satisfactory for the replacement of Pt. We confirmed in our previous report (K. Kwon et al., Catal Today, 232 (2014) 175) that the insufficient HOR activity of Pd could be supplemented by coupling with other elements or compounds such as Ru and tungsten oxide. To investigate the effect of alloying with Ru thoroughly, the calculation of hydrogen binding energy was performed on the basis of spin polarized density functional theory. Pure Pd(001) and Ru(001), Pd monolayer on Ru, and Pd bilayer on Ru are considered as model systems in the calculation. Strain and ligand effects are only applicable to bimetallic models (Pd monolayer on Ru and Pd bilayer on Ru). The negative sign of strain and ligand effects stands for a decrease in binding energy for PdRu alloy. Meanwhile, instead of making an effort to turn the model alloy systems into nanoparticles of Pd mono/bilayer on Ru, which would not be realistic in a few nm dimension, the actual confirmation of HOR enhancement at the level of half cell and PEMFC single cell was obtained by fabricating homogeneous PdRu alloy nanoparticles on carbon support. PdRu nanoparticles of different Pd:Ru atomic ratios of 1:0, 9:1, 1:9, and 0:1 were characterized with TEM and XRD, and compared with a commercial state-of-the-art Pt-based anode catalyst (PtRu1.5/C) in electrochemical experiments. The PdRu9 catalyst shows the highest HOR activity among the PdRu samples, which is comparable to the PtRu catalyst, even though the respective Pd and Ru have lower activity than PtRu. The highest HOR activity of the Ru-richest PdRu nanoparticles could be in line with the highest HOR activity of the Ru-richest PdRu model system (Pd monolayer on Ru).