To investigate the role of abnormal protein expression of the tumor metastasis related-genes in invasion and metastasis of nasopharyngeal cancer (NPC) and to seek the metastasis-related markers for NPC, high-throughput tissue microarray and immunohistochemistry were used to detect protein expression of membrane type 1-matrix metalloproteinase (MT1-MMP), membrane type 2-matrix metalloproteinase (MT2-MMP), membrane-cytoskeletal crosslinker Ezrin (Ezrin), metastasis suppressor gene nm23-H1, the epithelial cell adhesion molecule E-cadherin (E-cad)and tissue inhibitor of metalloproteinase-2 (TIMP-2) in NPC. Results showed that significant high expression of MT1-MMP and Ezrin proteins and very low expression of nm23-H1 and TIMP-2 proteins were found in NPC compared with non-cancerous nasopharyngeal epithelium (P < 0.05, P < 0.01, respectively). Expression of MT1-MMP, MT2-MMP and Ezrin proteins in the stageⅡ, stageⅢ and Ⅳ NPC and NPC with lymph node metastasis is significantly higher than that of in the stageⅠ NPC and NPC without lymph node metastasis (P < 0.05, P < 0.01 respectively), but expression of nm23-H1 protein in the stageⅡ, stageⅢ and Ⅳ NPC and NPC with lymph node metastasis is significantly lower than that of in the stageⅠ NPC and NPC without lymph node metastasis (P < 0.05). There were significantly positive correlation between MT1-MMP and MT2-MMP (r = 0.308, P < 0.001), nm23-H1 and E-cad(r = 0.167, P < 0.05), nm23-H1 and TIMP-2(r = 0.279, P = 0.001); E-cad and TIMP-2(r = 0.279, P = 0.001) in the NPC. Also, there were obviously negative correlation between MT1-MMP and E-cad(r = -0.188, P < 0.05), MT1-MM and TIMP-2(r = -0.233, P < 0.05), Ezrin and E-cad (r = -0.204, P < 0.05) in NPC. Based on the cluster analysis, there was common higher expression of MT1-MMP, MT2-MMP and Ezrin proteins in the NPC than that of in the chronic inflammatory nasopharyngeal epithelium (P < 0.05). However, common higher loss expression of nm23-H1, E-cad and TIMP-2 proteins were found in NPC compared with the peri-cancer nasopharyngeal epithelium and chronic inflammatory nasopharyngeal epithelium (P < 0.05, P < 0.01). Logistic regression analysis and validity estimation indicated that MT1-MMP gene might be better independent prognostic value for metastasis and clinical progress of NPC. The results suggested that high protein expression of multiple metastasis related-genes, low expression of the metastasis suppressor genes and loss balance between metastasis genes and metastasis suppressor genes might play important role in the metastasis and clinical progression of NPC. MT1-MMP protein can be used as the better independent prognostic molecular marker for metastasis of NPC.