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Background: Tight junction proteins (TJPs) play a role in epithelial defense mechanisms. However, the effect of Helicobacter pylori (Hp) on TJPs remains unclear. This study aimed to evaluate the expression of TJPs in relation to Hp infection and eradication in gastric carcinogenesis. Methods: In total, 510 subjects (284 controls and 226 gastric cancer [GC] patients) were prospectively enrolled in the study. The expression of claudin‐1 and ‐2 (CLDN‐1, ‐2), occludin (OCLN), and tight junction protein 1 (TJP1) was measured based on their Hp infection status in normal corpus mucosa and evaluated following Hp eradication using quantitative real‐time polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Results: The expression of TJP1 in Hp+ controls was significantly lower than that in Hp− controls (p = 0.006), whereas it was higher in Hp+ than in Hp− GC patients (p = 0.001). Moreover, the increased expression of TJP1 in Hp+ GC patients was reduced to levels in Hp−within a year after Hp eradication and was maintained for more than 5 years. Furthermore, IHC results for TJP1 were similar to qPCR results. In particular, the higher IHC staining intensity of TJP1 in the cytosol of GC patients (p = 0.019) decreased after Hp eradication (p = 0.040). Conclusion: Hp infection affects TJP expression. The high expression of TJP1 in Hp+ GC patients was restored to control levels after Hp eradication, suggesting that TJP1 plays a role in gastric carcinogenesis. [ABSTRACT FROM AUTHOR]