Nasopharyngeal carcinoma (NPC) is a common malignancy in South China.Cancer stem cells (CSCs) are thought as the key players in the resistance to chemo-or radio-therapy.In this study, we found that the expression of IAP family proteins increased in nasopharyngeal carcinoma stem cells and plays an important role in maintaining nasopharyngeal cancer stem cell properties.We designed and synthesized a novel Smac mimetic compound, APG-1387 that promoted the rapid degradation of cIAP1/2 and XIAP in NPC stem cells.Our results showed that APG-1387 decreased proportion of nasopharyngeal carcinoma stem cells, nasosphere formation.Moreover,APG-1387 promoted autophagic degradation of Sox2 through promoting Sox2 sumoylation, which is an important stem cell transcription factor in NPC.These fimdings support the use of APG-1387 for the therapeutic treatment of NPC cancer stem-like cells and warrant further clinical evaluation.