Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne disease caused by Nairovirus, and it is sometimes characterized by reactive hemophagocytic histiocytosis (HLH). The reasons for reactive HLH are macrophage-activating syndrome and disseminated intravascular coagulation due to cytokine storm, liver dysfunction, and endothelial damage by the virus. In this study, the effectiveness of high-dose methylprednisolone (HDMP) (5 to 30 mg/kg/d), fresh frozen plasma (FFP), and intravenous immunoglobulin (IVIG) was investigated in patients with CCHF associated with reactive HLH. Twelve patients with CCHF in association with reactive HLH were included in the study. The patients were successfully treated with HDMP to suppress the macrophage activation, FFP to treat disseminated intravascular coagulation, and IVIG to treat severe thrombocytopenia. No patients received ribavirin. Fever reduced in 1.6 ± 0.8 days, WBC count increased above 4.500/µL in 4.0 ± 2.4 days, platelet count increased above 150.000/µL in 8.5 ± 2.5 days, and D-dimer level decreased under 1 mcg/dL in 5.8 ± 3.6 days. Consequently, HDMP, FFP, and IVIG may be effective in patients with CCHF associated with reactive HLH during hemorrhagic period of the disease.