Background: Bitter taste receptors (T2Rs), especially T2R38s appear as innovative regulators of innate immunity in the respiratory system. The single nucleotide polymorphisms (SNPs) in TAS2R38 gene may contribute to individual differences in susceptibility to respiratory infections especially chronic rhinosinusitis (CRS). TAS2R38 genotypes distribution varies by geographic region, race and ethnicity. The aim of the preliminary study was the identification of SNPs in TAS2R38 encoding genes in Polish patients with CRS and finding potential correlation with CRS phenotypes. Material and methods: The preliminary study contained 20 CRS patients undergoing functional endoscopic sinus surgery (FESS). Fresh sinus mucosa (SM) was obtained during FESS in CRS patients. Patients were genotyped for TAS2R38 using Sanger method and the genotype occurrences of the clinically recalcitrant CRS cohort was evaluated. Analysis of TAS2R38 expression in SM of CRS patients was performed using immunohistochemistry (IHC). Results: T2R38 was highly expressed in SM of CRS patients. Patients with CRS demonstrated both common genotypes PAV, AVI. The heterozygotes frequency (AVI/PAV) was the highest. The protective genotype (PAV/PAV) was noticed in the lowest frequency and connected with lower average value of CT score compare to AVI/AVI genotypes (p=0.01). Conclusions: The work presented in this study provides the hypothesis that airway bitter T2Rs are an innovative sphere of human respiratory innate protection. TAS2R38 polymorphism may influence the susceptibility to CRS. The AVI haplotypes are an independent risk factors for CRS. Additionally, the bitter taste receptors and related signalling pathways might create an unique group of therapeutic targets to treat CRS.