In the present work, we demonstrate that the mechanism and kinetics of CO 2 activation, as the first step of its hydrogenation, over supported nickel catalysts is particle size sensitive owing to the distinct H 2 dissociation ability over nickel particles with various sizes. Large nickel nanoparticles facilitate H 2 dissociation, enabling CO 2 activation via a kinetically favored redox mechanism compared to small nickel nanoparticles that activate CO 2 via the formate mechanism. The elucidation of the dependency of the catalytic reaction pathway on particle size will guide the rational design of supported nickel catalysts for selective CO 2 hydrogenation. This work demonstrated in the CO 2 hydrogenation reaction, CO 2 is activated through different mechanisms due to different H 2 dissociation capabilities over supported Ni catalysts with different particle sizes, which provides a convincing experimental explanation for the structural sensitivity of nickel-based catalysts.