ObjectivesAs a critical component of the epithelial barrier, tight junctions (TJs) are essential in nasal mucosa against pathogen invasion. However, the function of TJs has rarely been reported in nasal inverted papilloma (NIP). This study aims to investigate the potential factors of TJs' abnormality in NIP.MethodsWe assessed the expression of ZO‐1, occludin, claudin‐1, claudin‐3, and claudin‐7 in healthy controls and NIP by real‐time quantitative polymerase chain reaction and immunofluorescent staining. The correlation between TJs expression and neutrophil count, TH1/TH2/TH17 and regulatory T cell biomarkers, and the proportion of nasal epithelial cells was investigated.ResultsUpregulation of ZO‐1, occludin, claudin‐1, and claudin‐7, along with downregulation of claudin‐3, was found in NIP compared to control (all p < 0.05). An abnormal proportion with a lower number of ciliated cells (control vs. NIP: 37.60 vs. 8.67) and goblet cells (12.52 vs. 0.33) together with a higher number of basal cells (45.58 vs. 124.00) in NIP. Meanwhile, claudin‐3 was positively correlated with ciliated and goblet cells (all p < 0.01). Additionally, neutrophils were excessively infiltrated in NIP, negatively correlated with ZO‐1, but positively with claudin‐3 (all p < 0.05). Furthermore, FOXP3, IL‐10, TGF‐β1, IL‐5, IL‐13, and IL‐22 levels were induced in NIP (all p < 0.01). Occludin level was negatively correlated with IL‐10, IL‐5, IL‐13, and IL‐22, whereas ZO‐1 was positively with TGF‐β1 (all p < 0.05).ConclusionNasal epithelial barrier dysfunction with TJs anomalies is commonly associated with abnormal proliferation and differentiation of epithelial cells and imbalance of immune and inflammatory patterns in NIP.Level of EvidenceNA Laryngoscope, 2023