Background: Toll-like receptor-7 (TLR7) plays pivotal roles in type I interferon (IFN) secretion and protective antiviral immunity against hepatitis C virus (HCV) infection. Objectives: To assess expression levels of TLR7 in patients with hepatitis C infection and patients with hepatocellular carcinoma (HCC), to investigate possible association between TLR7 (rs179009) polymorphism and infection outcome, and to compare the expressions of TLR7 variants. Methodology: A total of 98 candidates, divided into four groups, were enrolled in this study. TLR7 mRNA expression level was determined for all participants using real-time PCR, and TLR7 single nucleotide polymorphism (SNP) rs179009 was assessed using Taq-Man SNP genotyping assay and real-time PCR. Results: TLR7 expression levels were significantly lower in patients with chronic HCV and HCC compared to patients who naturally cleared their infection and controls (P< 0.05). In females, the AA genotype and the A allele were significantly predominant in HCV clearance group (83.33%), healthy controls (78.6%) and HCC patients (75%), compared to females with chronic hepatitis (21.4%) (P< 0.05), while, the AG and GG genotypes were more commonly found in chronic HCV-infected females. However, no association was found regarding TLR7 polymorphism genotypes distribution in males and HCV susceptibility. High TLR7 expression levels were associated with the AA genotype in HCV-infected females and males. Conclusion: HCV may induce down regulation of TLR7 expression. Polymorphisms in TLR7 gene with different expression levels might affect immune response during HCV infection.