Thermo, pH, and photo triple-responsive hollow nanospheres self-assembled from amphiphilic random copolymer poly (styrene-stat-4-vinylpyridine) (PS-stat-P4VP) and azobenzene (AZO) 4-phenylazophenol have been investigated by means of TEM, SEM, FTIR, DLS and UV-vis spectrophotometry. Controlling over the ratio of PS-stat-P4VP and AZO can realize different size of hollow nanospheres. PS-stat-P4VP/AZO hollow nanospheres display UCST behavior and perform well reversible self-assembly and disassembly property between 25 degrees C and 45 degrees C as well as pH = 2.7 and pH = 8.1. Besides, the hollow nanospheres can be significantly elongated along the polarization direction of the polarizer, showing well photo-responsive performance. With the UCST of about 37 degrees C and pH responsive range close to human body, those PS-stat-P4VP/AZO hollow nanospheres demonstrate great potential in medicine and physiology.