Secretion on the surface of human nasal mucosa contains many innate proteins, the key factors of which are SPLUNC1 and LPLUNC1, members of the palate, lung and nasal epithelium clone (PLUNC) family. These two proteins are highly expressed in nasopharyngeal epithelium with the relative specificity. Both of them have bacterial/permeability-increasing protein (BPI) domain which can bind to lipopolysaccharide (LPS) to inhibit or kill bacterial growth directly. They also have the immuno defense function to protect nasopharyngeal epithelium from Epstein-Barr virus (EBV) and some other pathogenic microorganism effectively. These proteins play a significant role in the process of chronic inflammation and carcinogenesis of nasopharyngeal epithelium by inhibiting the secretion of inflammatory factors, such as IL-6, through activating NF-κB and STAT3 signaling pathways. In addition, they also can suppress nasopharyngeal carcinoma (NPC) cell growth and induce cell apoptosis through MAPK and miR-141-PTEN-AKT signaling pathways when the PLUNC proteins are re-expressed in NPC cell lines. Further study about the mechanism of PLUNC protein family in pathogenesis of NPC has important significance for the prevention and treatment guidance of NPC.