OBJECTIVE To explore the role of p15 protein in the pathogenesis of poorly differentiated nasopharyngeal carcinoma (NPC). METHODS Using immunohistochemical LSAB (Labeled Streptavidin Biotin method), we examined 55 samples of poorly differentiated NPC and 15 samples of nasopharyngeal normal tissue for expression of p15 protein. RESULTS The p15 protein expression was located in the cytoplasm and nuclear membranes. The positive rate of p15 protein in NPC is significantly lower than that in normal tissue (P < 0.05). Important correlations were found between the p15 protein expression and clinic stages, T classification of NPC. But p15 protein wasn't correlated to neck lymph node metastasis and 5-years survival rate. CONCLUSIONS The absence of p15 protein may play an important role in the pathogenesis and development of NPC, the expression of p15 protein may be used to evaluate the biological behavior of NPC.