Abstract: Objective To investigate the potential of IL-6 as a therapeutic target for recurrent nasopharyngeal carcinoma. The main purpose of this study is to observe the expression of angiogenic associated factors during nasopharyngeal carcinoma (NPC) stem cell early stage differentiation and its effect on angiogenesis clone cells. Methods The secretion of cytokine IL-6 during nasopharyngeal carcinoma (NPC) stem cell early stage differentiation and VEGF was detected by ELISA. The IL-6,HIF-1α,STAT3 and VEGF expression levels were measured by Real time PCR and Western blot before and after IL-6 interference. The colony forming ability of HUVECs made by cell supernatant of different groups was detected by plate colony formation assay. Results Compared with poor differentiation NPC cell line CNE-2 and undifferentiated NPC cancer stem cells CNE-2S, the early differentiation stage NPC cancer stem cells secreted more IL-6 and VEGF, exhibited enhanced expression of IL-6,HIF-1α,STAT3 and VEGF. After silencing IL-6 gene expression through its specific siRNA, those cells obviously reduced the expression of HIF-1α、STAT3、VEGF genes. Cell culture media of early stage differentiation NPC cancer stem cells showed stronger ability to promote HUVEC colony formation than other groups, this promotion ability was sharply decreased with IL-6 gene silencing. Conclusion The findings suggest that IL-6 can be a therapeutic target for nasopharyngeal carcinoma and a reference for clinical treatment.NPC cancer stem cells enhanced angiogenic association factors during early differentiation stage and promoted angiogenesis in this period.