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In order to modulate the drug release profiles, the hierarchical mesoporous silica nanoparticles (HMSNs) are fabricated by a two-step synthetic process. The HMSNs exhibit uniform spherical morphology with nanoscaled size, well mono-dispersed size distribution, and smooth surface. Because of the hierarchical pore structures with different mesoporous sizes and morphologies (partial open and partial blocked pores), the HMSNs can release the loaded drug in a controlled manner. The hierarchical mesoporous structures directed drug release profiles suggest a feasible strategy to tailor drug release behaviors. Meanwhile, the HMSNs exhibit good biocompatibility. Therefore, the HMSNs having tailorable drug release capacity would be a potential candidate to improve their therapeutic efficiency for drug delivery systems.