For catalysts comprised of mixed manganese-chromium oxides MnxCr3-xO4 (x = 0.3–2.7) prepared by Pechini route with Ni and Ru supported by impregnation fundamental factors determining their performance in ethanol steam reforming have been elucidated using combination of structural (XRD, HRTEM), spectroscopic (UV–vis), surface science (XPS, FTIR spectroscopy of adsorbed CO) and kinetic (H2 and EtOH TPR, oxygen isotope heteroexchange with C18O2) methods. The most important feature is strong metal-support interaction stabilizing small clusters of metals/alloys and preventing carbon nucleation. The lattice oxygen mobility and reactivity increased with Mn content. The highest TOF was obtained for (Ni + Ru)–loaded oxide support containing cubic spinel phase of MnCr2O4 composition, which implies a positive effect of Ni-Ru interaction in mixed clusters on catalytic activity. This catalyst has also a high density of active sites, surface enriched by Mn and sufficient oxygen mobility providing coking stability, which makes it attractive for practical application.