Objectives: Crimean-Congo hemorrhagic fever (CCHF) is a tick borne zoonotic infection. Up till now knowledge about pathogenesis of the disease is limited. Cytokine response is quite important during this infection. The aim of this study was to determine the serum tumor necrosis factor-alpha (TNF-&alpha;) and the interleukin-4 (IL-4) levels in patients with CCHF and compare with those of healthy controls. Materials and methods: Forty-two adult CCHF patients and 40 healthy subjects were included in this study. The diagnosis of CCHF was based upon anti-CCHF virus IgM positivity (ELISA method), and/or positivity in real time-polymerase chain reaction (RT-PCR) in acute phase serum samples. Serum TNF-&alpha; and IL-4 levels were determined by ELISA method. Results: In patients with CCHF the mean serum TNF-&alpha; level was significantly higher than the control group (15.01 vs. 7.69 pg/ml; p<0.05) and also the mean serum IL-4 levels were significantly higher than the control group (1.07 vs. 0 pg/ml; p<0.05). Conclusion: The levels of serum TNF-&alpha; and IL-4 in CCHF patients were found higher than healthy controls. These cytokines might play an important role in the pathogenesis of CCHF.