The ability to construct supported metal catalysts with high dispersion at high metal loadings is of crucial importance. There are two great challenges to be overcome in order to achieve this goal: the issue of stability of the support material with high surface areas and abundant mesopores at working conditions, and the issue of metal nanoparticles agglomeration upon harsh treatments, especially for transition metals that are difficult to reduce and aggregate easily. To overcome these problems, here we propose a new and promising strategy for encapsulating the Ni nanoclusters (d = 5.6 nm) into/onto the uniform and inter-connected intra-mesopores (7–8 nm) of single-crystalline HBEA, achieving highly dispersive Ni nanoparticles (content: 40 wt%, dispersion: 3.5%) on the stable carrier. The architecture of relative position of the Ni nanoparticles and support is directly revealed by ultrathin sections transmission electron microscopy and N2 sorption measurements, presented together with the indirect evidences of temperature programmed reduction of H2 and IR spectroscopy of adsorbed CO. In comparison to such an advantageous structure of metal and support, the Ni nanoparticles are more commonly deposited on the limited external surface or inter-mesopores of commercial HBEA carriers. Besides, the novel catalyst shows superior adsorption performance towards large molecules. As expected, the catalyst leads to a significantly high initial rate of 132 mmol g−1 h−1 (equivalent to 38 g g−1 h−1) and highly selective octadecane formation (96% yield) from stearic acid conversion. Consequently, high activity and stable durability are realized for four recycling runs of drainage oil hydrodeoxygenation with the newly developed Ni/HBEA. [ABSTRACT FROM AUTHOR]