Background: The Na+/K+-ATPase pump plays a vital role in maintaining the osmotic balance between intracellular and extracellular compartments. This study is designed to reveal possible differences of Na+/K+-ATPase activity, Na+/K+-ATPase α1 protein expression, and total ATPase (Na/K ATPase, Ca ATPase, H/K ATPase) activity in cell membranes of nasal mucosa with polyps. Methods: Patients who were diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) for the first time were included in study group. Patients who underwent bilateral endoscopic sinus surgery (ESS) for reasons other than chronic sinusitis constituted the control group. Uncinate mucosa was sampled without local/topical anesthesia. Na+/K+ ATPase α1 protein level was measured by ELISA, and total ATPase activity and Na+/K+ ATPase activity by the colorimetric method. Results: There was no statistically difference between Na+/K+-ATPase α1 protein expression values between the study and control groups (P>0.683). Total ATPase activity was lower in nasal polyp patients without significance (P>0.140). Na+/K+-ATPase activity was significantly lower in nasal polyp patients when compared to the control group (P<0.033). In male patients, Na+/K+-ATPase activity and total ATPase activity were significantly lower in the study group (P<0.016 and P<0.020). Conclusions: Decreased Na+/K+-ATPase activity may be involved in the etiology of CRSwNP, by means of changing osmotic balance. In addition, the significant decrease in Na+/K+-ATPase activity and total ATPase activity in male CRS patients with nasal polyps suggests that there may be gender (or hormonal) differences in the etiology of CRSwNP. Key Points: Decreased Na+/K+-ATPase activity may be involved in the etiology of CRSwNP. The significant decrease in Na+/K+-ATPase activity and total ATPase activity in male CRS patients with nasal polyps suggests that there may be gender (or hormonal) differences in the etiology of CRSwNP. Key words: Ca2+ ATPase, H+/K+ ATPaz, Nasal polyp, Chronic Rhinosinusit, Na+/K+-ATPase, Na+/K+-ATPase α1 protein expression, total ATPase Key Points: Decreased Na+/K+-ATPase activity may be involved in the etiology of CRSwNP. This study might contribute to solve the therapeutic challenges in CRSwNP which might be due to unexplained physiopathology of nasal polyposis.