Magnesium hydride (MgH2) has been considered to be one of the most promising solid-state hydrogen storage materials owing to its high hydrogen capacities, excellent reversibility and abundant source. However, the high dehydrogenation energy barrier and poor kinetics embarrass the practical application of MgH2 in fuel cell. Doping nano-catalyst is deemed to be the most effective method to improve kinetics property of hydrogen storage materials, but the nanoparticles generally suffer from agglomeration and inactivation during the cycling hydrogen storage. Here we present a promising strategy to facilely prepare a high-efficiency transition metal oxide nano-catalyst, TiO2 nanoparticles, in which monodispersed single-crystal-like TiO2 nanoparticles are wrapped with amorphous carbon. The in-situ synthesized TiO2 nanoparticles/amorphous carbon catalyst exhibit superior catalytic effect on the dehydrogenation properties of MgH2. A significant reductions of hydrogen desorption temperature (163.5 °C) and activation energy (69.2 kJ mol−1) have been obtained for the TiO2 nanoparticles/amorphous carbon catalyzed MgH2, which can be fully rehydrogenated with a reversible capacity of about 6.5 wt% at 200 °C within 5 min, and then completely dehydrogenated at 275 °C within 10 min. It is demonstrated that such significantly improved hydrogen desorption properties can be attributed to the in-situ formation of TiO2 nanoparticles, amorphous carbon and multi-valance Ti species, which play the synergistically catalytic roles in the nano-catalyst. In particular, the presence of amorphous carbon in the catalyst can not only prevent the aggregation and growth of catalyst nanoparticles, but also dramatically reduce the desorption energy value of H in MgH2, according to the density functional theory calculation. This finding opens a new venue for the synthesis of monodispersed single-crystal-like TiO2 nanoparticles/amorphous carbon catalyst with high-activity, safety, low cost, and its practical application in MgH2 and other hydrogen storage systems.