In the present study, we observed that several ISGs with known or proposed anti-CCHFV activity, i.e., Mx1, ISG15 and ISG20 or not defined for CCHFV like IFIT1, IFIT3, IFITM3, IFI16, and OAS3 were upregulated in the acute phase CCHFV patient samples as well as in the cell-infection model. Here, IFI16 is linked to infection.