Cytokines play a key role in the regulation of immune responses. In hepatitis C virus infection (HCV), the production of abnormal cytokine levels appears to contribute to the progression of the disease, viral persistence, and affects response to therapy. Cytokine genes are polymorphic at specific sites, and certain polymorphisms located within coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines. The aim of the present study was to identify potential markers of cytokines genes associated with the susceptibility to HCV infection. The cohort was composed of 128 individuals infected by HCV and 94 healthy controls. Genotyping was carried out by PCR‐SSP. The distributions of the following polymorphisms were compared in these groups: TNF‐α (−308G/A [rs1800629]), TGF‐β1 (codon 10 T/C [rs1982073], codon 25 G/C [rs1800471]), IL‐10 (−1082 A/G [rs 1800896]; −819T/C [rs1800871]; −592A/C [rs 1800872]), IL‐6 (−174G/C [rs1800795]), and IFN‐γ (+874T/A [rs2430561]). This study demonstrated a statistically significant difference in the frequency of TGF‐β1 codon 25 polymorphism between healthy subjects and those infected with HCV. No associations were observed between polymorphisms of TNF‐α, IFN‐γ, IL‐10, TGF‐β1 codon 10, and IL‐6 and HCV infection. These findings suggest that TGF‐β1 codon 25 polymorphism could be a host genetic factor associated with susceptibility to HCV infection. J. Med. Virol. 80:58–64, 2008. © 2007 Wiley‐Liss, Inc.