Exploration of new methodologies to tune catalytic selectivity is a long-sought goal in catalytic community. In this work, oil-water interfaces of Pickering emulsions are developed to effectively regulate catalytic selectivity of hydrogenation reactions, which was achieved via a precise control of the spatial distribution of metal nanoparticles at the droplet interfaces. It was found that Pd nanoparticles located in the inner interfacial layer of Pickering droplets exhibited a significantly enhanced selectivity for p-chloroaniline (up to 99.6%) in the hydrogenation of p-chloronitrobenzene in comparison to those in the outer interfacial layer (63.6%) in pure water (68.5%) or in pure organic solvents (46.8%). Experimental and theoretical investigations indicated that such a remarkable interfacial microregion-dependent catalytic selectivity was attributed to the microenvironments of the coexistence of water and organic solvent at the droplet interfaces, which could provide unique interfacial hydrogen-bonding interactions and solvation effects so as to alter the adsorption patterns of p-chloronitrobenzene and p-chloroaniline on the Pd nanoparticles, thereby avoiding the unwanted contact of C-Cl bonds with the metal surfaces. Our strategy of precise spatial control of catalysts at liquid-liquid interfaces and the unprecedented interfacial effect reported here not only provide new insights into the liquid-liquid interfacial reactions but also open an avenue to boost catalytic selectivity.