Ovarian cancer is the ffth leading cause of cancer-related deaths among women. In particular, it is a high cause of mortality among women in industrialized countries. Human epididymis protein 4 (HE4) has recently emerged as a serological biomarker for the diagnosis of ovarian cancer. Herein, we report the ultrasensitive detection of HE4 using a gold (Au) nanoplate (NPl)-based surface-enhanced Raman scattering (SERS) immunoassay, wherein a capture antibody-immobilized Au NPl acts as an immune substrate and detection antibody-immobilized Au nanoparticles (NPs) serve as immunoprobes. The presence of the target biomarker (HE4) results in the formation of a sandwich structure of Au NPls and NPs, providing strong SERS signals. The developed method allows us to detect HE4 at low concentrations of 10 -17 M. The selective detection of HE4 was verifed using the Au NPl SERS immunoassay. We anticipate that the current approach could be helpful for the early diagnosis of ovarian cancer and eventually applied for diverse biomarker detection.