Nanotechnology has attracted much attention because it possesses many advantages to engineer new organized nanomaterials and endow them with improved performance. In recent decades, mesoporous silica nanoparticles (MSNs) have been proven to be excellent solid supports owing to their superior properties. Molecular and supramolecular switches have also received a lot of interest in the past decade on account of their unique features. Materials derived from the combination of MSNs as solid supports and molecular/supramolecular switches as movable entities have emerged in the literature and are playing prominent roles in materials science nowadays. Thus, in this review, we chose to gather significant and typical examples of intelligent materials, which comprise MSNs surface-immobilized with molecular and supramolecular switches, and overview their wide applications in many fields such as controlled release of cargo molecules for disease therapy and cell imaging. Utilizing the switching ability of molecular and supramolecular switches, smart hybrid nanomaterials are endowed with intelligently controllable properties in response to a variety of external stimuli such as pH variation, enzyme, light irradiation, temperature, redox, magnetic field, competition, and ultrasound. In order to rationalize the presentation concisely, we will introduce molecular switches and supramolecular switches cooperated with MSNs based on their different features and the actuations they are responsive for.