A novel structure with high surface enhanced Raman scattering (SERS) activity and bio-specificity as a SERS-based immuno-sensor (named as Raman reporter-labeled immuno-Au aggregate) is demonstrated and employed for protein detection. In each fabrication process, the features of those aggregates are obtained and characterized by ultraviolet-visible (UV-Vis) extinction spectra, transmission electron microscopy (TEM) images, scanning electron microscopy (SEM) pictures, and SERS spectra. Experimental results indicate that proper amounts of the reporter molecules can result in the moderate aggregation morphologies of gold nanoparticles. Compared with the previously reported method using Raman reporterlabeled immuno-Au nanoparticles, more sensitive SERS-based protein detection is realized with this novel immuno-sensor.