COVID-19 pandemic has caused severe public health crisis worldwide. To prevent the adverse health effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on people in various countries, different types and production processes of SARS-CoV-2 vaccines, including live attenuated, nucleic acid, virus vectored, inactivated and recombinant protein vaccines, primarily focusing on viral surface spike protein, have been successively developed. This review describes the structure, function and immunological properties of the SARS-CoV-2 spike protein, as well as the research status, safety and applicability of spike protein-related SARS-CoV-2 vaccine, and discusses solutions for potential issues.