HCV is a blood pathogen that affects approximately 180 million people worldwide. It has the ability to escape its host’s defense mechanism and is considered a resistant species. Toll-like receptors (TLRs) are a family of evolutionary receptors that have been identified by the diagnosis of pathogens as the main regulators of innate and acquired immune responses. Studies have shown that genetic changes in the TLR3 gene are associated with high susceptibility or resistance to immune and infectious diseases. In this study, the effects of the TLR3 gene single nucleotide polymorphism rs78726532 on susceptibility to HCV infections were examined. The association between this polymorphism and the risk of hepatitis C in 50 patients and 50 healthy subjects was investigated. The results revealed a significant relationship between polymorphism rs78726532 and hepatitis C infection (p = 0.002). Thus, it could have a therapeutic and predictive potential.