Here, a highly specific, sensitive, and reliable immunoassay has been developed based on surface-enhanced Raman scattering for quantitative detection of carcinoembryonic antigen (CEA). A novel hollow gold nanospheres (HGNs) was firstly fabricated by seed-mediated methods instead of the one-step methods with high homogeneity and then, the monodispersed HGNs were embedded with 4-mercaptobenzonic acid to form surface-enhanced Raman scattering (SERS) tags and magnetic microspheres were synthesized as enrichment substrates. Based on this sandwich immunoassay strategy, CEA monoclonal antibody -conjugated HGNs-based SERS tags and CEA polyclonal antibodies -conjugated magnetic microspheres were used to detect CEA up to 100 ng/mL with a detection limit of 10 pg/mL, which were two orders of magnitudes lower than that of GNSs-based SERS tags. The monodispersed HGNs were desirable SERS tags for quantitative sandwich immunoassay assay, showing strong potential for the clinical diagnosis of cancer biomarkers.