We report the synthesis and catalytic activities of highly stable, hollow nanoreactors, called SiO2/Pd/h-ZrO2, which consist of silica microsphere (SiO2)-supported Pd nanoparticle multicores (Pd) that are encapsulated with a hollow and nanoporous ZrO2 shell (h-ZrO2). The SiO2/Pd/h-ZrO2 nanoreactors are fabricated by first synthesizing SiO2/Pd/SiO2/ZrO2 microspheres, and then etching the inner SiO2 shell with dilute NaOH solution. The hollow and nanoporous ZrO2 shell of the nanoreactors serves two important functions: 1) it provides reactants direct access to the Pd nanoparticle multicores inside the SiO2/Pd/h-ZrO2 nanoreactors during catalysis, and 2) it stabilizes the Pd nanoparticles or protects them from aggregation/sintering. The fabrication of such structures capable of protecting the Pd nanoparticles from aggregation/sintering is of particular interest considering the fact that Pd nanoparticles generally have a high tendency to aggregate because of their high surface energies. Furthermore, the structures are interesting because the Pd nanoparticles are designed and synthesized here to have ‘naked’ surfaces or no organic surface-passivating ligands—that are often necessary to stabilize metallic nanoparticles—in order to increase their catalytic efficiency. The resulting SiO2/Pd/h-ZrO2 nanoreactors show excellent catalytic activity, as shown in the hydrogenation of olefins and nitro groups, even at room temperature under moderate hydrogen pressure. This stems from the SiO2/Pd/h-ZrO2 microspheres’ high surface area and their small, stable, and bare Pd nanoparticles. Furthermore, the SiO2/Pd/h-ZrO2 nanoreactor catalysts remain fairly stable after reaction and can be recycled multiple times without losing their high catalytic activities.