Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant tumor derived from the nasopharyngeal epithelium and is mainly prevalent in Southern China and Southeast Asia countries. Cisplatin (DDP) provides the first-line therapeutic administration in NPC patients. However, chemoresistance has been a main barrier and caused bad treatment outcome in NPC therapy. To understand the molecular mechanism of acquired resistance to DDP, multiple methods were performed to examine the morphocytology and molecular changes in DDP-resistant NPC cells. We found that drug resistance cells displayed epithelial-mesenchymal transition (EMT) characteristics. DDP-resistant NPC cells exhibited enhanced migration and invasion potential. Moreover, overexpression of TAZ, one key gene in Hippo pathway, is closely associated with the DDP resistance of NPC cells and its EMT properties. Depletion of TAZ in DDP-resistant cells reversed EMT phenotypes to MET characteristics and restored chemosensitivity of DDP-resistant cells to DDP treatment. These results suggest that inactivation of TAZ could be a promising approach for the treatment of NPC patients.