Core-shell structured SiO2/poly(N-isopropylacrylamide) (SiO2/PNIPAM) microspheres were successfully fabricated through hydrolysis and condensation reaction of tertraethyl orthosilicate (TEOS) on the surface of PNIPAM template at 50 ~C. The PNIPAM template can be easily removed by water at room temperature so that SiO2 hollow microspheres were finally obtained. The transmission electron microscope and scanning electron microscope observations indicated that SiO2 hollow microspheres with an average diameter of 150 nm can be formed only if there are enough concentration of PNIPAM and TEOS, and the hy- drolysis time of TEOS. FTIR analysis showed that part of PNIPAM remained on the wall of SiO2 because of the strong interaction between PNIPAM and silica. This work provides a clean and efficient way to prepare hollow microspheres.