The metastasis and recurrence of nasopharyngeal carcinoma (NPC) contribute to the poor prognosis of patients. Inhibiting epithelial-mesenchymal transition (EMT) is an effective strategy to obstruct metastasis. Therefore, this study aimed to explore the effects of Capn4 on the EMT of NPC cells and its specific mechanism of action. The mRNA and protein expression levels of objective genes in NPC cell lines (5-8F and CNE-2) were evaluated by qRT-PCR and western blotting methods. The subcellular localization of Capn4 was detected by immunofluorescence (IF). Migration and invasion abilities of NPC cells were examined via wound-healing and trans-well methods, and the linkage between Snail and its downstream effector gene (claudin-11) was validated by chromatin immunoprecipitation (ChIP), dual-luciferase, and the yeast one-hybrid assays in series. Over-expression of Capn4 activated the PI3K/AKT signaling pathway and improved the expression of Snail, thus promoting the migration and invasion abilities of NPC cells. Mechanically, claudin-11 is one of the target genes in NPC cells that Snail regulates in a transcriptional regulatory manner. By blocking the regulatory axis of CAPN4/AKT/Snail/claudin-11 can significantly inhibit the invasion and metastasis of NPC cells. Capn4 promoted the EMT of NPC cells by activating the PI3K/AKT/Snail/claudin-11 axis, thereby promoting the malignant development of NPC. The Capn4/PI3K/AKT/Snail/claudin-11 axis might be a novel target to prevent NPC progression.