Here we show that "off-on" type of photodynamic therapy agents could be developed using hollow mesoporous silica nanoparticles (HMSNPs), which can be used not only for enhancing delivery of photosensitizers to cancer cells but also for enabling switchable optical properties of the photosensitizers. Fluorescence and singlet oxygen generation of the photosensitizer-loaded HMSNP are turned off in its native state. In vitro cell studies showed that this HMSNP-based "off-on" agent may have potential utility in selective fluorescence detection and photodynamic therapy of cancers.