Prohibitin-1 (PHB, also known as PHB1) is a pleiotropic protein in cells. PHB is a cell-surface receptor and is involved in the regulation of proliferation, apoptosis, transcription, and mitochondrial protein folding. PHB is upregulated in 5-8F cells, which overexpress LPLUNC1 (long palate, lung, nasal epithelium clone 1, a candidate tumour suppressor gene), and was identified using two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS/MS). Thus, we examined PHB mRNA levels using 24 nasopharyngeal carcinoma (NPC) and eight normal nasopharyngeal epithelium (NPE) tissues. Protein levels were detected using immunohistochemistry with a tissue microarray consisting of 323 NPC and NPE tissues. A Kaplan-Meier analysis was carried out, and the log-rank test was used to determine the statistical significance of the results using SPSS 15.0 software. PHB mRNA and protein expression levels were significantly downregulated in NPC tissue specimens compared with the NPE samples (P<0.01). In addition, decreased PHB expression correlates significantly with a poor prognosis, whereas decreased PHB protein expression is closely associated with advanced clinical stage and metastasis in NPC lesions. Therefore, we favour the hypothesis that the expression level of PHB could be used as a potential prognostic biomarker for NPC.