Lichen planus (LP) is a chronic inflammatory disease that affects skin and mucous membranes of squamous cell origin. LP probably represents a cell-mediated immunologic response to an induced antigenic change in the skin or mucosa. The etiology of OLP is unclear in most instances, however HCV may be implicated. Numerous studies have suggested that cytokine gene polymorphisms may influence the outcome of HCV-infected OLP patients. Interferon-gamma (IFN-ɤ) is a T-helper1 cytokine involved in the activation of cellular immunity. This cytokine maintains the expression of major histocompatibility (MHC) class II by keratinocytes, thereby contributing to disease onset and chronicity of OLP. IL-8 gene has been associated with the susceptibility of individuals to OLP, as well as the progression and prognosis of this disease. The aim of this study was to investigate the presence of SNPs rs4073 and rs2430561 in IL-8 and IFN-γ genes respectively and investigate their association with HCV-related OLP and to disease severity.The present study included 60 subjects, divided into four groups of 15. The groups were as follows: OLP patients positive for HCV infection, OLP patients with no HCV infection, HCV patients with no oral lesions and subjects with no HCV infection no oral lesions. Analysis was doneusing real-time PCR, and consequent melting curve analysis was performed on LightCycler® 2.0 Instruments for identification of polymorphisms in −251 A/T (rs4073) in the promoter region of IL-8 gene and +874 T/A (rs2430561) in exon 1 in IFN-ɤ gene.This study found that HCV infection can act as an aggravating factor for OLP, making those patients 11 times more prone to develop erosive type of OLP. IFN-γ rs2430561 T>A genotype frequencies showed no difference between cases and controls. As for IL-8 rs4073 A>T, there was no significant difference in genotype and frequency among the 4 studied groups. Additionally, there was no significant difference in genotype frequency after subgrouping the 30 OLP patients into erosive and non-erosive types. However, the A-allele of IL-8 rs4073 A>T was significantly higher in patients with OLP than in those without. Furthermore, OLP patient having both HCV infection and the A-allele of IL-8 rs4073 A>T, would be more prone to develop erosive OLP 16 times than other patients with only one or no risk factors.In conclusion, HCV infection is a contributing factor to the development of erosive OLP. IFN-γ rs2430561 T>A has no significant role in the clinical severity of OLP. The A-allele of IL-8 rs4073 A>T may have a role in the development and progression of OLP.