Novel catalysts based on precious and non-precious catalytic centers, as well as support materials are currently under investigation all over the world. The improvement of oxygen reduction reaction (ORR) on Pt-based catalysts is strongly related to its dispersion and interaction with the substrates. [1]^,[2] The tolerance to small organics is also influenced by the electronic modification of the catalytic center itself or induced by the substrate.[3] A variety of carbon-based substrates such as carbon nanotubes (CNT), graphite (HOPG), graphene, carbon nanohorns (CNH),[4] various graphitic domains of MWCNT, and non-carbonaceous based materials, such as metal oxides (Titania, doped-Titania, Yttria, Ceria, etc.) [5]^,[6]can be used as both catalyst and catalyst support materials. On the way to further explore the substrate effect on non-precious electrocatalyst, CoSe₂was supported on Carbon, CNH and nitrogen doped nanohorn (NCNH). The activity of non-Pt catalysts was found to be strongly dependent on the surface composition of substrate materials. The improved interaction of modified substrate and the metal centers (either precious or non-precious) modify the active reaction centers of the electrocatalyst, which in turn boost the catalytic activity towards molecular oxygen reduction with minimum overpotential. The analysis indicates that the improved activity measured in half-cells was validated in microfluidic fuel cells. Acknowledgements Authors acknowledge the partial support of the European Union’s Seventh Framework Programme (FP7/2007-2013) for the Fuel Cell and Hydrogen Joint Technology Initiative under grant agreement nr 303492 CathCat. SM U acknowledges Raman-Charpak fellowship, JMMH, J.M.M.-H., C.A. C.-R., and L.A. E-W acknowledge financial support from CONACYT-Mexico Nr.: MX-351743; MX-561206; MX-234729. [1] Y. Luo, N. Alonso-Vante, Electrochim. Acta, doi: 10.1016/j.electacta.2015.04.098. [2] J. Ma, A. Habrioux, Yun Luo, G. Ramos-Sanchez, L. Calvillo, G. Granozzi, P. B. Balbuena, N. Alonso-Vante, J Mater. Chem. A, Submitted; J. Ma, A. S. Gago, W. Vogel, N. Alonso-Vante, Chemcatchem, 2013, 5, 701-705. [3] J. Ma, A.S. Gago, W. Vogel, N. Alonso-Vante, Tailoring and Tuning the Tolerance of a Pt Chalcogenide Cathode Electrocatalyst to Methanol, ChemCatChem, 5 (2013) 701-705. [4] Sreekuttan M. Unni, J. M. Mora-Hernandez, Sreekumar K., N. Alonso-Vante, ChemElectroChem, Submitted. [5] C.Liu , Y.Wei and K.Wang, Chem.Comm., 2010, 46, 2483-2485. [6] Y. Luo, A. Habrioux, L. Calvillo, G. Granozzi, N. Alonso-Vante, ChemCatChem, doi: 10.1002/cctc.201500130.