Introduction:  IL-8 is one of the pro-inflammatory cytokines which can play an essential role in the pathogenesis of chronic rhinosinusitis (CRS) as well as nasal polyposis (NP). The ability of individuals in producing IL-8 is partially determined by IL-8-251 A/T polymorphism. Hence, the aim of the present study was to investigate the association between IL-8-251 A/T and CXCR2 +1208 C/T genes polymorphisms and susceptibility to CRS and NP. Materials and Methods: Two hundred and forty fiveCRS patients and 204 healthy controls were included in this study. CRS patients were categorized by the existence or absence of NP. IL-8 promoter-251 A/T and CXCR2 +1208 C/T gene polymorphisms were genotyped via the allele specific PCR (AS-PCR) method. Results: While no remarkable difference was demonstrated between patients and controls for both CXCR2 +1208 C/T and IL-8 -251 A/T polymorphisms, a significant increase in IL-8-251 AA genotype was detected in CRS patients with NP compared to those without it (29.3% and 16.2%, respectively; P=0.03). Interestingly, this association got far stronger when only non-asthmatic CRS patients were taken into consideration (P=0.001). Conclusion: The results of the present study indicate that the inheritance of IL-8-251 Aallele is associated significantly with NP development in CRS patients. Therefore, NP formation might be a result of the exposure to an intense inflammatory environment, which is more likely in genetically susceptible CRS patients.