Mesoporous silica nanoparticles show promise as a drug-carrier vehicle for biomedical applications, but the development of simple, biocompatible capping systems has remained a challenge. We have found that lysozyme molecules can act as a pH-responsive nanovalve to block and unlock the pore entrances of MCM-41 nanoparticles for guest molecules. Our experiments indicate that pore blocking is due to a pH-induced conformational change by which the effective size of the protein is changed in a reversible manner. This effect may form the basis of a controlled-release system without the need to functionalize the pore mouth and caps.