The elucidation of the ring-opening reaction mechanism is a critical step towards improving the catalytic performance for the conversion of biomass into value-added chemicals. Herein, we focused on the stepwise C–O bond hydrogenolysis mechanism of oxygen-containing heterocycles (O-heterocycles) into α,ω-diols, in particular THFA to 1,5-PeD, over selective Ni-La(OH)3 in hydrogen-donor isopropanol. A mechanistic study was carried out on a structurally well-defined Ni-La(OH)3, where the mechanism was elucidated using a combination of kinetic and 13C NMR isotope labeling experiments. It was suggested that both Ni nanoparticles and La(OH)3 support play a critical role in the reaction mechanism, where basic hydroxide species of the support initially deprotonate the CH2OH and –OH modified furan, tetrahydrofuran and tetrahydropyran rings, adsorbing them chemically on the catalyst surface. This step is followed by a direct hydride attack on the second carbon atom of these rings, which is proposed to be the key step for ring cleavage, as indicated by the increased deuteration at this position. It is assumed that a catalytic transfer hydrogenolysis reaction (CTH) reaction of THFA is proposed to proceed via the dehydrogenation of isopropanol over isolated Ni species, forming hydrogen species that can be adsorbed on the Ni surface or desorb as H2.