Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case fatality rate that is caused by infection with the recently identified tick-borne SFTS virus (SFTSV), for which there are no specific countermeasures. We examined the effects of ribavirin and mizoribine, which are nucleoside analogue drugs with broad antiviral activities, on SFTSV proliferation in vitro. When 3 cell lines were treated with these drugs before and during infection with a Chinese SFTSV strain, the 99% effective concentrations (EC99) of ribavirin were 19-64 μg/ml (78-262 μM); in contrast, the EC99 of mizoribine was >500 μg/ml (1,929 μM). Similar levels of inhibitory effects of ribavirin were observed with 4 Japanese SFTSV strains. However, when Vero cells were treated with ribavirin 3 days after inoculation, the inhibitory effect was dramatically decreased, indicating that ribavirin did not effectively reduce virus production in pre-infected cells. These results suggest that ribavirin could be used as post-exposure prophylaxis for the prevention of SFTS.