The main reasons of catalysts deactivation in hydro-processing pyrolysis liquids are by coke deposition, poisoning by bio-oil impurities (S, N, K, Cl, etc.), leaching of catalyst components, structural degradation in the presence of H2O, and sintering. The deactivation of catalysts by the acidity of the pyrolysis liquid is a specific concern, and this deactivation mechanism was studied by treating newly developed NiCuMo-SiO2 catalysts in 1 M acetic acid water solution (pH = 2–3). The activity of the acid-treated catalysts was subsequently investigated in the hydrodeoxygenation of gaseous propionic acid, in a tubular reactor at 225 °C with n-hexane and n-octane serving as diluent and internal standard, respectively. The samples treated by acid at different times (15–360 min) were characterized by X-ray diffraction (XRD), high resolution transition electron microscopy (HRTEM), X-ray fluorescence (XRF), CO chemisorption, N2 physical adsorption, and X-ray photoelectron spectroscopy (XPS). XRF and HRTEM studies together with the residual mass of catalyst pointed out at gradual leaching of catalyst components. Among the catalyst components, dissolution of nickel was the most pronounced, while molybdenum content decreased to a lesser extent. This is due to the formation of more acid stable molybdenum blues. The amount of copper decreased only slightly, due its higher electrochemical potential. Oxidation of metalliс species Cu and Ni is shown to obtain Cu2O, NiO and Ni(OH)2-like phases. Interestingly, the acidic treatment resulted in increasing active surface of the catalyst, nevertheless, the catalyst activity in propionic acid conversion irreversibly decreased in time by the acetic acid treatment due to loss of the active components (substantially nickel).