Enzymes are characterized by an active site that is typically embedded deeply within the protein shell thus creating a nanoconfined reaction volume in which high turnover rates occur. We propose nanoparticles with etched substrate channels as a simplified enzyme mimic, denominated nanozymes, for electrocatalysis. We demonstrate increased electrocatalytic activity for the oxygen reduction reaction using PtNi nanoparticles with isolated substrate channels. The PtNi nanoparticles comprise an oleylamine capping layer that blocks the external surface of the nanoparticles participating in the catalytic reaction. Oxygen reduction mainly occurs within the etched channels providing a nanoconfined reaction volume different from the bulk electrolyte conditions. The oxygen reduction reaction activity normalized by the electrochemically active surface area is enhanced by a factor of 3.3 for the nanozymes compared to the unetched nanoparticles and a factor of 2.1 compared to mesoporous PtNi nanoparticles that possess interconnecting pores.