In this work, the first example of a hierarchically structured hollow silica system is reported without any chemical modification to the enzyme involved in the process. The leaching of the physically adsorbed enzyme is substantially restrained in comparison to pure hollow silica supports. The hierarchical architecture is composed of the ordered hollow silica spheres with a shell-in-shell structure. This rationally integrated architecture, which serves as the host for glucose oxidase immobilization, displays many significant advantages, including increases in mechanical stability, enzyme loading, and bioactivity, and a decrease in enzyme leaching compared to existing pure hollow silica matrices. This facilitates further multifarious applications for enhanced enzyme immobilization, biosensors, and biocatalysis.