Significance Small spaces in nanoreactors may have big implications in chemistry, because the chemical nature of molecules and reactions within the nanospaces can be changed significantly due to the nanoconfinement effect. Two-dimensional (2D) nanoreactor formed under 2D materials can provide a well-defined model system to explore the confined catalysis. We demonstrate a general tendency for weakened surface adsorption under the confinement of graphene overlayer, illustrating the feasible modulation of surface reactions by placing a 2D cover on top of the surface. The developed concept “catalysis under cover” can be applied to reactions between two opposite 2D walls interacting with each other through van der Waals force, which helps to design high-performance nanocatalysts interfacing with 2D material overlayers.