A novel well-defined amphiphilic fluorescent polymer containing asymmetric perylene bisimide was designed and synthesized by combining reaction of perylene anhydride with amino functional polyhedral oligomeric silsesquioxane (POSS) and atom transfer radical polymerization (ATRP) of N-isopropylacrylamide (NIPAM). All the intermediate and final products were characterized by NMR, Fourier transform infrared spectroscopy (FT-IR), elemental analyses, and gel permeation chromatograph (GPC). Self-assembly of the amphiphilic polymers was investigated in aqueous solution and POSS-containing hybrid nanoparticles were obtained and characterized by dynamic laser light scattering (DLS) and transmission electron microscopy (TEM). The novel hybrid nanoparticles exhibit attractive high red fluorescence at 645 nm due to the significant effect of the bulky POSS moieties. Moreover, based on the thermoresponsive PNIPAM coronas, the fluorescence intensity of the self-assembled hybrid nanoparticles can be further enhanced and tuned by changing temperature.