ABSTRACT Occludin is the first identified protein in the tight junction (TJ), but its function has remained for the most part obscure. TJs have been demonstrated to play important roles in the inner ear function, and occludin is expressed in all the epithelial TJs in the inner ear. Thus, we examined the inner ears of occludin-deficient (Occ−/−) mice. Although inner ears initially developed normally in Occ−/− mice, apoptosis occurs in hair cells in the organ of Corti around day 12 after birth, and deafness develops. Since hair cell degeneration was not observed in cochlear explant cultures of Occ−/− mice, environmental changes were considered to be the trigger of cell death. As for the vestibular system, both the morphologies and functions are normal in Occ−/− mice. These phenotypes of Occ−/− mice are very similar with those of claudin-14 or claudin-9 deficient mice, leading us to speculate on the existence of imbalance induced by TJ abnormalities, such as localized ionic components. Moreover, the occludin deficiency led to dislocalization of tricellulin, a gene responsible for human deafness DFNB49. The deafness in Occ−/− mice may be due to this dislocalization of tricellulin.