YAP signaling has been reported to be dysregulated in numerous cancer types. However, its roles in nasopharyngeal carcinoma (NPC) are poorly understood. Although several studies have shown that FOXC2 promotes the progression of NPC, the underlying molecular mechanism remains largely unknown. Here, we have shown that FOXC2 interacted with YAP and TEAD, and activated YAP signaling. Furthermore, FOXC2-YAP signaling positively regulated the expression of Hexokinase 2 (HK2) and promoted the glycolysis. Moreover, the inhibitor of HK2, 3-BrPA effectively inhibited the tumorigenesis of NPC cells in vitro and in vivo. Collectively, our study demonstrated that FOXC2 promoted the glycolysis in progression of NPC by activating YAP signaling, and suggested that FOXC2 might be promising therapeutic target.