Ai-Yue Zhao,1 Yi-Jun J Dai,1 Jian-Feng Lian,2 Yan Huang,1 Jian-Guang Lin,1 Yang-Bin Dai,1 Tian-Wen Xu1 1Department of Medical Oncology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, China; 2Department of Anesthesiology, Quanzhou Children’s Hospital, Quanzhou 362000, China Background: Yes-associated protein (YAP), a key player of the Hippo pathway, has been identified to have more and more important roles in tumorigenesis and may be an important biomarker for cancer therapy. YAP is important for bladder cancer cell migration, metastasis, and drug resistance; however, its function in bladder cancer stem cells remains unknown. Purpose: The aim of this work was to examine the expression and role of YAP in bladder cancer stem cells. Materials and methods: We identified that the expression level of YAP was significantly enriched in bladder cancer stem cells compared to noncancer stem cell population. Moreover, the effect of YAP on stem cell self-renewal was examined in bladder cancer cells by siRNA silencing approach. In addition, we showed that YAP is required for aldehyde dehydrogenase activity in bladder cancer cells. Results: RNAseq analysis and quantitative real-time PCR results showed that silencing of YAP inhibited the expression of ALDH1A1 gene. Conclusion: Collectively, our findings for the first time elucidated that YAP serves as a cancer stem cell regulator in bladder cancer, which provided a promising therapy strategy for patients with bladder cancer. Keywords: bladder cancer, YAP, ALDH1, cancer stem cells