This paper describes the development of composite nanoparticles. A novel composite nanoparticle has been prepared by an in situ polymerization method. The nano-CdS has been prepared, then the polymerization of acrylic acid (AA) was carried out by initiator potassium persulfate (KPS) under ultrasonic irradiation. The surface of the composite nanoparticles was covered with abundant carboxylic groups (–COOH). The nanoparticles are water-soluble, stable and biocompatible. Reaction of the composite nanoparticles with proteins results in an enhanced resonance light scattering (RLS) at 380 nm. Based on this, a new resonance light-scattering (RLS) method was developed for the determination of proteins including BSA, HSA and human γ-IgG. Under the optimum conditions, the enhanced RLS intensity is linearly proportional to the concentration of proteins. The liner range is 0.1–15 μg mL −1 for HSA, 0.2–20 μg mL −1 for BSA and 0.1–50.0 μg mL −1 for human γ-IgG, respectively. The method has been applied to the determination of the total protein in human serum samples collected from the hospital and the results are in good agreement with those reported by the hospital. This method proved to be very sensitive, rapid, simple and tolerant of most interfering substances.