Crimean-Congo hemorrhagic fever (CCHF) is a viral zoonosis. Toll-like receptors (TLRs) initiate signaling cascades leading to the activation of the innate immune system following CCHF infection. In this study, TLR7 (Gln11Leu, c.4-151A/G, and +1817G/T) polymorphisms were investigated in CCHF patients using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). The study population comprised 149 CCHF patients and 171 controls. For the TLR7 Gln11Leu polymorphism, there was no significant difference between the case and control groups in allele (P=0.144) and genotype frequencies (P=0.219). In the TLR7 IVS1 +1817G/T polymorphism, a statistically significant difference was found in allele frequencies (P=0.026), but there was no significant difference in the TLR7 c.4-151A/G polymorphism (P=0.310). There was a statistically significant difference in the distribution of the TLR7 c.4-151GG genotypes frequencies between patients and controls (P=0.042; OR=2.23). Furthermore, there were statistically significant associations between the TLR7 c.4-151A/G polymorphism and both severe disease and patient mortality (P<0.001 and P=0.047, respectively). The TLR7 IVS1 +1817TT genotype was also significantly associated with the case group but not the control group (P=0.045). A strong positive linkage among TLR 7 variants was found using haplotype analysis. The incidence of two haplotypes, AGG and AGT, was determined to exhibit significant differences between the case and control groups (P<0.001 and P<0.001, respectively). These findings suggest that the TLR7 IVS1 +1817G/T and TLR7 c.4-151A/G polymorphisms may be important in the susceptibility or clinical course of CCHF disease. J. Med. Virol. 87:1090-1095, 2015. (c) 2015 Wiley Periodicals, Inc.