Surface-enhanced Raman spectroscopy (SERS) technology has been widely used in viral molecular detection due to its high sensitivity, simple operation and rapid detection. The research of virus detection by Raman technology at home and abroad mainly focuses on the detection of the SERS spectrum of viral nucleic acids and various bases that make up the nucleic acids, and detection of viral proteins is rare. In this paper, the S protein of the new coronavirus (SARS-CoV-2) is used as the detection object, and with the label-free SERS detection method, the ordinary Raman spectra of solid and saturated liquid S protein of the SARS-CoV-2 and the SERS spectra of the low-concentration S protein of SARS-CoV-2 on the substrate of gold nanoparticles with a size of 40 nm are compared. The results show that it is completely feasible to use SERS technology to detect the S protein of SARS-CoV-2 on the substrate of 40 nm gold nanoparticles. The carboxyl groups in the S protein molecule of SARS-CoV-2 and gold nanoparticles are molecularly enhanced, and the amino groups and gold nanoparticles are electromagnetically enhanced, so that the Raman effect of the S protein of the SARS-CoV-2 is enhanced and the peak position is moved to a certain extent. The experiments obtained relatively good SERS spectra of the low-concentration S protein of SARS-CoV-2, which provides a method for the establishment of a sensitive, specific and rapid detection technology for the S protein of the SARS-CoV-2.