Poly(styrene-acrylic acid) nanoparticles were prepared by emulsifier-free emulsion polymerization under ultrasonic irradiation and characterized by IR and TEM. The results show that the average diameter of the nanoparticles is 9 nm. The resonance light scattering peak was at 340 nm and it was greatly enhanced by protein. The nanoparticles are stable, water-soluble and bioactivity. A high sensitive RLS probe for protein determination was proposed.