Monodisperse organic/inorganic composite microspheres with well-defined structure were prepared through the encapsulation of silica coated superparamagnetic magnetite colloidal nanoparticle clusters (CNCs) with cross-linked poly(N-isopropylacrylamide) (PNIPAM) shell. At first, the sub-micrometer-sized CNCs were fabricated by the solvo-thermal process, and then a silica layer was coated oil the Surface of CNCs through a sol-gel process, and finally, a thermoresponsive shell of PNIPAM was deposited onto the surface of the core/shell magnetic microspheres by a precipitation polymerization. The experimental results showed that the size of Fe3O4 core, the thickness of SiO2 shell, as well as volume phase transition temperature (VPTT) of PNIPAM shell could be well controlled, and this structured modulation could satisfy different requirements. The superparamagnetic behavior, high magnetization (the saturation magnetization of Fe3O4/SiO2/PNIPAM microspheres with a 10% cross-linking density is 41.6 cmu/g), and good thermosensitivity make these composite microspheres ail ideal candidate for various important applications such as ill controlled drug delivery, bioseparation, and catalysis.