Abstract: Although great progress has been made in the screening of clinical therapeutic drugs for corona virus disease 2019（COVID-19） and the research and development of vaccines related to severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）, the lack of specific drugs for SARS-CoV-2 is still the key problem facing the prevention and treatment of COVID-19. RNA interference is considered as an antiviral mechanism independent of interferon system in mammals. Currently, great progress has been made in the research and development of various antiviral small interfering RNA（siRNA） drugs. In this paper, the status of RNA interfe-rence in mammalian immune system, the defects of current clinical therapeutic drugs for COVID-19 and related vaccines in epidemic prevention and treatment, the research progress of siRNA drugs in coronavirus treatment and the potential challenges of clinical application of related drugs are reviewed. While evaluating the application prospect of siRNA drugs as COVID-19 clinical therapeutic drugs, the challenges faced by related drug research and development are analyzed.