Aldehyde dehydrogenase 1 (ALDH1) has been considered to be a marker for cancer stern cells. However, the role of ALDH1 in head and neck squamous cell carcinoma (HNSCC) has yet to be determined. In this study, we isolated ALDH1-positive cells from HNSCC patients and showed that these HNSCC-ALDH1(+) cells displayed radioresistance and represented a reservoir for generating tumors. Based on microarray findings, the results of Western blotting and immunofluorescent assays further confirmed that ALDH1(+)-line-age cells showed evidence of having epithelial-mesenchymal transition (EMT) shifting and endogenously co-expressed Snail. Furthermore, the knockdown of Snail expression significantly decreased the expression of ALDH1, inhibited cancer stern-like properties, and blocked the tumorigenic abilities of CD44(+)CD24(-)ALDH1(+) cells. Finally, in a xenotransplanted tumorigenicity study, we confirmed that the treatment effect of chemoradiotherapy for ALDH1(+) could be improved by Snail siRNA. In summary, it is likely that ALDH1 is a specific marker for the cancer stern-like cells of HNSCC. (C) 2009 Elsevier Inc. All rights reserved.