Background: The occurrence of nasal polyps is related to mucosal barrier damage. The role of MG53, an important epithelial repair regulator, in nasal polyps remains unclear. This study aimed to investigate the role of MG53 in nasal epithelial repair. Methods: We divided the patients into the following three groups (n=15 each): chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP) and septal deviation (control). We performed qRT-PCR and western blotting to determine the expression of MG53, TGF-β1, Smad2/3, zonula occluden-1 (ZO-1), and collagen-a1 (Col-a1) in nasal tissues and human nasal epithelial cells (HNECs). HNECs were cultured to investigate the regulatory role of MG53 and the TGF-β1/Smad pathway in the repair of nasal epithelial cells. Results: We found that the expression of MG53, TGF-β1, Smad2/3, ZO-1, and Col-a1 was upregulated in the CRSsNP group, whereas it was downregulated in the CRSwNP group. In the HNECs of nasal polyps, the expression of TGF-β1, Smad2/3, ZO-1, and Col-a1 was downregulated after overexpressed MG53, whereas this was reversed by the knockdown of MG53. Additionally, we found that TGF-β1 stimulation resulted in significantly upregulated MG53 expression, which was impeded by TGF-β1 inhibitors. MG53 expression facilitated proliferation, promoted the secretion of Col-a1, and inhibited apoptosis in HNECs. Conclusion: MG53 inhibited the TGF-β1/Smad pathway and fibrosis, enhanced the proliferation of nasal epithelial cells, and supported nasal epithelial repair. The results of this study provide a new therapeutic regimen for the treatment of nasal polyps. Keywords: epithelial repair; mitsugumin53; nasal polyps; tight junction; TGF-β1/Smad.