A new hybrid nanoreactor framework with poly(ethylene oxide)-perforated silica walls is designed to encapsulate hollow manganese oxide nanoparticles (MONs) of high distinctness and homogeneity. Achieved by an interfacial templating scheme, the nanoreactor ensures that acidic etching of MONs by an acetate buffer solution is highly controlled for precise control of the hollow interior. As such, hollow MONs with different nanostructures are developed successfully through a facile acetate buffer solution etching. The resultant hollow MONs are integrated within the hybrid nanoreactor and demonstrate superior r(1) relativity of up to 2.58 mm(-1) s(-1) for T-1 magnetic resonance imaging (MRI). By modifying the nanoreactor architecture, it is also demonstrated that the efficacy of MONs as T-1 MRI contrast agents can be significantly improved if an optimal cluster of hollow MONs is encapsulated into the hybrid silica framework. The evolution of core morphology with time is studied to elucidate the etching mechanism. It is revealed that the hollow formation arises due to the surface stabilization of MONs by acetate ions and the subsequent acidic etching of the interior core in a sporadic manner. This is different from the commonly reported nanoscale Kirkendall effect or the selective etching of the core-shell MnO/Mn3O4 structure.