Hollow porous nanoparticles were proposed to transform the skin layer structure for enhancing the performance of reverse osmosis (RO) membrane in this work. Amino-modified hollow mesoporous silica nanospheres (AHMSS) with a size from 110 to 130 nm were successfully prepared via the hard template method. AHMSS were added in the organic phase and then incorporated into the RO membrane skin layer after the interfacial polymerization process. The hydrophilicity of RO membrane was improved by AHMSS. The performance evaluation results showed that AHMSS improved the RO membrane flux (improved by 41.5%) with rejection decreasing slightly. Amino-modified mesoporous silica nanospheres without hollow cores were also prepared and incorporated into the RO membrane skin layer to investigate the effects of the hollow cores of AHMSS on the membrane performance. The results showed that the hollow cores of AHMSS contributed to the improvement of membrane performance. This work demonstrates that AHMSS have huge potential in preparing RO membranes with both high flux and high rejection.