Cancer stem cells (CSCs) constitute a small population of undifferentiated cells within a tumor that have the ability to self-renew and drive tumor formation, thus behaving as cancer-initiating cancer cells. Therapeutic interventions that eliminate CSCs are necessary to completely cure patients, since CSCs are a crucial source of tumor recurrence and metastasis. An induced CSC-like (iCSCL) model was recently established using induced pluripotent stem cells (iPSCs). In this study, a natural product-eucommicin A-was identified from Eucommia ulmoides leaves by screening for anti-CSC activity using the iCSCL model. Its structure was elucidated by spectroscopic methods as a quinic acid diester of 3,4,3',4'-tetrahydroxy-β-truxinic acid. Eucommicin A exhibited selective anti-CSC activity and inhibited tumor sphere formation by iCSCL cells. The results of this study suggest that eucommicin A could serve as a lead compound in the development of drugs to abrogate the stemness and self-renewal ability of CSCs.