Novel thermally and magnetically dual-responsive mesoporous silica nanoparticles [magnetic mesoporous silica nanospheres (M-MSNs)-poly(N-isopropyl acrylamide) (PNIPAAm)] were developed with magnetic iron oxide (Fe 3 O 4 ) nanoparticles as the core, mesoporous silica nanoparticles as the sandwiched layer, and thermally responsive polymers (PNIPAAm) as the outer shell. M-MSN-PNIPAAm was initially used to control the release of sophoridine. The characteristics of M-MSN-PNIPAAm were investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetry, N 2 adsorption-desorption isotherms, and vibrating specimen magnetometry analyses. The results indicate that the Fe 3 O 4 nanoparticles were incorporated into the M-MSNs, and PNIPAAm was grafted onto the surface of the M-MSNs via precipitation polymerization. The obtained M-MSN-PNIPAAm possessed superparamagnetic characteristics with a high surface area (292.44 m 2 /g), large pore volume (0.246 mL/g), and large mesoporous pore size (2.18 nm). Sophoridine was used as a drug model to investigate the loading and release properties at different temperatures. The results demonstrate that the PNIPAAm layers on the surface of M-MSN-PNIPAAm effectively regulated the uptake and release of sophoridine.