Purpose The aim of this study was to investigate the possible role of raftlin (RFTN) in chronic rhinosinusitis with nasal polyps (CRSwNP). There is no study in the literature investigating the role of RFTN in the pathogenesis of CRSwNP. Methods The present study was designed as a case-control study and conducted between 25.09.2020 and 01.01.2022. CRSwNP and control groups were formed in the study. Serum and tissue samples were taken from each patient in the study and their RFTN levels were measured. While nasal polyps were used for tissue samples in the CRSwNP group, middle meatus mucosa obtained during concha bullosa surgery was used in the control group. Results The control group included 31 patients (8 female, 23 male) and the CRSwNP group included 49 patients (14 female, 35 male). The mean age of the control group was 40.42 +/- 9.99 years, while the mean age of the CRSwNP group was 43.47 +/- 10.19 years. When the groups are compared in terms of gender and age, there were no statistically significant differences (p = 0.78, p = 0.19, respectively). The serum RFTN levels in the control and CRSwNP groups were 7.85 +/- 10.87 ng/ml, and 7.02 +/- 8.59 ng/ml, respectively (p = 0.45). The tissue RFTN levels in the control group and CRSwNP group were 87.15 +/- 69.91 ng/ml, and 66.50 +/- 17.10 ng/ml, respectively (p = 0.04, statistically significant). Conclusion RFTN deficiency in nasal polyp tissue may be one of the reasons for the development of CRSwNP. Further studies are needed to elucidate the role of RFTN in CRSwNP.