A novel immunoassay based on surface-enhanced Raman scattering (SERS) has been developed. The method exploits the SERS-derived signal from reporter molecules (crystal violet, CV) encapsulated in antibody-modified liposome particles. The antigen is firstly captured by the primary antibody immobilized in microwell plates and then sandwiched by secondary antibody-modified liposome. The CV molecules are released from the liposome and transferred to specially designed substrate of gold nanosphere arrays with sub-10-nm gaps. The concentration of the antigen is indirectly read out by the SERS intensity of the CVs. The substrate used could substantially improve the sensitivity and reproducibility of SERS measurement. The SERS intensity responses are linearly correlated to logarithm of antigen concentration in the range of 1.0 x 10(-8) to 1.0 x 10(-4) gm L(-1) with a detection limit of 8 ng mL(-1). To our knowledge, this is the first report describing liposome-mediated enhancement of the sensitivity in immunoassay based on surface-enhanced Raman scattering. Experimental results show that the proposed method illustrates a potential prospect of applications in immunoassay.