Abstract Background: Claudin 4 is one of the tight junction proteins which considered one of the protective barriers that are mostly involved in the regulation of intercellular communication, paracellular transport and apical cell-to-cell adhesion. Overexpression of COX-2 and subsequent increase in prostaglandins (PGs) concentration have emerged in recent years as important players in cancer progression. Aim of Study: To explore immunohisto chemically the expression of both claudin-4 and COX2 in nasopharyngeal carcinoma and correlate their expression with each other and with different clinicopathological parameters. Material and Methods: This retrospective study was done upon formalin fixed, paraffin blocks of 32 nasopharngeal carcinoma cases and 6 non-neoplastic nasopharyngeal epithelium. The materials were obtained from archieves of Pathology Departement and Early Cancer Detection Unit (ECDU), Faculty of Medicine, Benha University during the years 2012- 2017. The immunohistochemical stain with Claudin 4 and COX2 was done and evaluated for each case. Results: High expression of claudin 4 was observed in 44% of studied nasopharyngeal cases with statistically significant correlation with tumor stage and distant metastasis (p