The activity and selectivity of structure-sensitive reactions are strongly correlated with the shape and size of the nanocrystals present in a catalyst. This correlation can be exploited for rational catalyst design, especially if each type of surface atom displays a different behavior, to attain the highest activity and selectivity. In this work, uniform Pd nanocrystals with cubic (in two different sizes), octahedral, and cuboctahedral shapes were synthesized through a solution-phase method with poly(vinyl pyrrolidone) (PVP) serving as a stabilizer and then tested in the hydrogenation of 2-methyl-3-butyn-2-ol (MBY). The observed activity and selectivity suggested that two types of active sites were involved in the catalysis those on the planes and at edges which differ in their coordination numbers. Specifically, semihydrogenation of MBY to 2-methyl-3-buten-2-ol (MBE) occurred preferentially at the plane sites regardless of their crystallographic orientation, Pd-(111) and/or Pd-(100), whereas overhydrogenation occurred mainly at the edge sites. The experimental data can be fit with a kinetic modeling based on a two-site Langmuir Hinshelwood mechanism. By considering surface statistics for nanocrystals with different shapes and sizes, the optimal catalyst in terms of productivity of the target product MBE was predicted to be cubes of roughly 3-5 nm in edge length. This study is an attempt to close the material and pressure gaps between model single-crystal surfaces tested under ultra-high-vacuum conditions and real catalytic systems, providing a powerful tool for rational catalyst design.