Objective To investigate the expression of forkhead box M1(FoxM1) transcription factor and cyclooxygenase-2 (COX-2) in nasopharyngeal carcinoma (NPC) tissues, and to discuss the related clinicopathological implications. Methods Immunohistochemistry method was used to examine the expression of FoxM1 and COX-2 in 80 NPC tissues and 40 normal nasopharyngeal mucosa tissues. The relationship of FoxM1 and COX-2 expression with the clinicopathological parameters of NPC was analyzed; we also analyzed the correlation between the FoxM1 and COX-2 expression. Results FoxM1 and COX-2 expressions were significantly higher in NPC tissues compared to normal nasopharyngeal mucosa tissues (FoxM1: 68.8% \[55/80\] vs 2.5% \[1/40\]; COX-2: 62.5% \[50/80\] vs 5.0% \[2/40\]; P<0.05). The expression of FoxM1 was significantly associated with lymph node metastasis (rs=0.252, P<0.05) and clinical stage of NPC (rs=0.230, P<0.05), and expression of COX-2 was also significantly associated with lymph node metastasis (rs=0.287, P<0.05) and clinical stage of NPC (rs=0.239, P<0.05). Furthermore, a positive correlation was observed between FoxM1 and COX-2 expression (rs =0.631, P<0.05), indicating a direct or indirect interaction between them. Conclusion Increased expression of FoxM1 and COX-2 in NPC tissues might be associated with the development and progression of NPC.