A pH and redox dual-responsive nanovalve with a long stalk was introduced on the surface of hollow mesoporous silica nanoparticles (HMSs-S1) to achieve cargo size selectivity delivery. The responsive nanovalve was designed by constructing of a stalk/beta-cyclodextrins (CDs) supramolecular complex, which is based on an acid-labile acetal group and the host-guest interactions between beta-cyclodextrins and ferrocenyl moiety (Fc). With stimulation by different pH and H2O2, Rhodamine 6G showed well-responsive behavior. On account of the long stalks of nanovalve, doxorubicin hydrochloride and 5-fluorouracil with different sized cargos are encapsulated in HMSs-S1 to test its behavior of cargo size-selective delivery. Moreover the HMSs-S2 with a short stalk based on beta-CDs/Fc inclusion complex is synthesized to load small sized 5-FU drug as contrast experiment. Compared with HMSs-S2, HMSs-S1 is compatible with larger drug molecules such as Rhodamine 6G (R6G) and doxorubicin hydrochloride (DOX), while small sized 5-fluorouracil (5-FU) is unable to be sealed by the nanovalve. Dual responsiveness and drug size selectivity make mechanized HMSs possess potential applications in drug delivery system. (C) 2016 Elsevier Inc. All rights reserved.