BACKGROUND: Recently, a new coronavirus spreads rapidly throughout the countries and resulted in a worldwide epidemic. Interferons have direct antiviral and immunomodulatory effects. Antiviral effects may include inhibition of viral replication, protein synthesis, virus maturation, or virus release from infected cells. Previous studies have shown that some coronaviruses are susceptible to interferons. The aim of this study was to evaluate the therapeutic effects of IFN-beta-1a administration in COVID-19. METHODS: In this prospective non-controlled trial, 20 patients included. They received IFN-beta-1a at a dose of 44 microg subcutaneously every other day up to 10 days. All patients received conventional therapy including Hydroxychloroquine, and lopinavir/ritonavir. Demographic data, clinical symptoms, virological clearance, and imaging findings recorded during the study. RESULTS: The mean age of the patients was 58.55 +/- 13.43 years. Fever resolved in all patients during first seven days. Although other symptoms decreased gradually. Virological clearance results showed a significant decrease within 10 days. Imaging studies showed significant recovery after 14-day period in all patients. The mean time of hospitalization was 16.8 +/- 3.4 days. There were no deaths or significant adverse drug reactions in the 14-day period. CONCLUSIONS: Our findings support the use of IFN-beta-1a in combination with hydroxychloroquine and lopinavir/ritonavir in the management of COVID-19. CLINICAL TRIAL REGISTRATION NUMBER: IRCT20151227025726N12.