One of the greatest challenges in developing protein chips is the detection of trace amounts of proteins on their surfaces. Traditionally employed techniques, such as optical microscopy and fluorescence, are effective and widely used, but it is sometimes hard to obtain fingerprint signals of biomolecules. In this paper, we use surface-enhanced Raman scattering (SERS) spectroscopy as a platform for protein detection. Micropatterned protein-mediated Au/Ag sandwich structures were employed as the detecting objects. Two types of proteins, pure hemoprotein and immunocomplex, were used as the media. Au/Ag layers were used as the SERS substrates. The resulting spectra showed good sensitivity and resolution. It indicates that SERS is a powerful tool in protein detection and has great potential for application in protein chips. Copyright © 2011 John Wiley & Sons, Ltd.