An immunoassay based on surface enhanced Raman scattering (SERS) has been developed using immuno-silver nanocubes (NCs) and silicon nanowires with high sensitivity. The features of the samples were characterized by XRD profiles, absorption spectra, SEM, TEM, and AFM images, EDS analyses, and SERS spectra. It was found that the obtained silver NCs maintained higher SERS activity than silver nanospheres. After the silver NCs were modified by an antibody and employed in immunoassay with silicon nanowire arrays as the substrate, the antigen concentration-dependent SERS spectra and dose-response calibration curves were obtained. The detection limit of a prostate-specific antigen in this immunosystem was as low as 2 × 10(-14) g ml(-1), attributing to the significant electromagnetic coupling effect generated between the densely packed silver NCs and the SERS-active silicon nanowire arrays. It can be inferred that this proposed strategy will show great advantages in sensitive immunoassay and other biochemical examinations.