● CD133 was significantly up-regulated in SP cells, which also demonstrated high chemoresistance and expression of ABCG2● Depletion of CD133 was associated with decreased SP frequency and attenuated in vivo tumor formation● Targeting CD133 together with cisplatin treatment abrogated the proliferation of SP cells in HNSCC, indicating that CD133 is a promising therapeutic target to overcome drug resistance in CSCs. This evidence concerns the gene PROM1 and neoplasm.