CeO2 nanocrystals (CN) with different morphologies (i.e., cube, octahedron, and rod) are prepared and the facet-dependent effect of these CeO2 nanocrystals on the adsorption and dephosphorylation of phosphorylated molecules is investigated for the first time using the model p-nitrophenyl disodium orthophorphate (p-NPP). Due to their different surface atomic configurations, the {111} and {110} facets have much higher adsorption capacity and kinetic catalytic activities than {100} facets. All the CeO2 nanocrystals can intensely promote the dephosphorylation reaction owing to the strong interaction between Ce cations and phosphoryl oxygens resulting in the cleavage of phosphoester bonds. As was expected, the above facet-dependent effect can be verified by the practical application results of the CeO2 nanocrystals on the capture and dephosphorylation of phosphopeptides. Thus, surface engineering could be a useful and feasible strategy for not only fundamentally understanding the interaction between crystal facets and molecules but also effectively developing high-performance functional materials.