Adaptive silver films (ASFs) have been studied as a substrate for protein microarrays. Vacuum evaporated silver films fabricated at certain range of evaporation parameters allow fine rearrangement of the silver nanostructure under protein depositions in buffer solution. Proteins restructure and stabilize the ASF to increase the surface-enhanced Raman scattering (SERS) signal from a monolayer of molecules. Preliminary evidence indicates that the adaptive property of the substrates make them appropriate for protein microarray assays. Head-to-head comparisons with two commercial substrates have been performed. Protein binding was quantified on the microarray using the streptavidinCy3/biotinylated goat IgG protein pair. With fluorescence detection, the performance of ASF substrates was comparable with SuperAldehyde and SuperEpoxy substrates. Additionally, the ASF is also a SERS substrate and this provides an additional tool for analysis. It is found that the SERS spectra of the streptavidinCy5 fluorescence reporter bound to true and bound to false sites show distinct difference.