Stimuli-responsive silica nanoparticles have emerged as a promising platform for the targeted and controlled delivery of therapeutic agents in cancer therapy. These nanoparticles possess unique physicochemical properties that allow for the stimuli-triggered release of loaded cargos, such as drugs, enzymes, oligonucleotides, photosensitizers, and metals. The stimuli-responsive nature of these nanoparticles enables them to respond to specific internal and external signals within the tumor microenvironment, including pH, temperature, and redox potential, among others. This leads to the enhanced targeting of cancer cells and improved therapeutic efficacy while minimizing the off-target effects. This review highlights recent advances in the development and application of stimuli-responsive silica nanoparticles for the delivery of multiple active agents for cancer therapy. Overall, stimuli-responsive silica nanoparticles offer great potential for the development of more effective cancer therapies with improved selectivity and reduced side effects.