The present study was aimed to determine twist expression in nasopharyngeal carcinoma (NPC) and to investigate the clinicopathological significance in the progress of NPC. Semiquantitative RT-PCR and Western blotting were carried out to investigate the expression of Twist in NPC cell lines and normal nasopharyngeal epithelial cell line, which showed that both Twist mRNA and protein were up-regulated in the tumor cells in comparison with the normal cells. We then examined Twist mRNA expression in non-cancerous nasopharyngeal mucosa (10 cases) and NPC (95 cases) using in situ hybridization. The results showed that Twist was overexpressed in 59 of 95 (62.1%) NPC samples. In contrast, there was no obvious expression of Twist mRNA in non-cancerous tissues. In addition, another 75 NPC samples were analyzed by immunohistochemistry, and 33 of the 75 samples were shown to be positive for Twist protein. Both Twist mRNA expression and Twist protein expression were positively associated with lymph-node metastasis and distant metastasis. Furthermore, expression of Twist protein was correlated with the NPC prognosis. Patients with NPC who were Twist protein-positive had a worse 5-year survival rate. These findings demonstrate that the Twist may play an important role in the invasion and metastasis of NPC. Twist protein is valuable marker for assessing the prognosis of NPC.