How to achieve supported metal nanocatalysts with simultaneously enhanced activity and stability is of vital importance in heterogeneous catalysis and remains a challenging goal. In this work, a surface defect-promoted Ni nanocatalyst with a high dispersion and high particle density embedded on a hierarchical Al2O3 matrix was fabricated via a facile method involving an in situ reduction process, which exhibits excellent activity and stability simultaneously for the reaction of CO2 methanation. HRTEM, HAADF-STEM, EXAFS, and positron annihilation spectroscopy demonstrate the existence of abundant surface vacancy clusters that serve as active sites, accounting for the significantly enhanced low the temperature activity of the supported Ni nanoparticles. In addition, the anchoring effect from support gives rise to a high reaction stability, without sintering and/or aggregation of active species during long-term use.