An unique, sensitive, and highly specific immunoassay system using gold nanoparticles and Surface-Enhanced Raman Spectroscopy (SERS) is described. To demonstrate the analytical capabilities of the new technique, Raman reporter (DTNB) that is coimmobilized with biospecific anti-protein A on gold nanoparticles (AuNP). Anti-protein A-AuNP-DTNB, which combing both electromagnetic field and chemical enhancement, was used to exploits the SERS-derived signal. A dynamic range of 2-3 orders of magnitude and 1-10 pg/mL of detection limitation of protein A were achieved. The results indicated this new technique could be used in clinical diagnostic applications with fast, high sensitivity and highthroughput screening of antibodies.