Nanocarriers are one of the key elements to improve the therapeutic potential of signaling molecules, including genes for the disease treatment and tissue repair. Here, a nanocarrier system is reported that delivers genetic molecule small interference RNA (siRNA) for osteoblastic stimulation. For this, a hollow form of mesoporous silica nanoshell (MSns) is designed to load and release siRNA to silence Plekho-1 gene. In particular, a pressure-induced loading method is effective in enhancing the incorporation of siRNA within a hollow space; a loading level attained approximate to 30% is almost three times higher than that of a non-hollow form. Furthermore, the release of siRNA from the nanocarriers is highly sustainable; continued over 18 d in a diffusion-controlled manner, in striking contrast to the rapid release (3 d) from a non-hollow form. The nanocarriers exhibit excellent cell viability, and the siRNA-nanocarrier complexes are efficiently internalized to osteoblastic cells (uptake level over 90%). The intracellular delivery suppresses the target gene Plekho-1 expression down to 20%, which in turn up-regulates the expression of osteoblast transcriptional factors (Runx2 and Smad2), demonstrating an effective gene delivery system for bone repair.