--- - |2- Colorectal cancer (CRC) is one of the most lethal and rampant human malignancies in the world. Zerumbone, a sesquiterpene isolated from subtropical ginger, has been found to exhibit an antitumor effect in various cancer types. However, the effect of Zerumbone on the biological properties of CRC, including epithelial‐mesenchymal transition (EMT) and cancer stem cells (CSCs) has not been fully elucidated. Here, we investigated the inhibitory action of Zerumbone on the EMT process, CSC markers, and the β‐catenin signaling pathway in the presence or absence of miR‐200c. The effect of Zerumbone on HCT‐116 and SW‐48 cells viability was examined by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide assay. The effects of Zerumbone on EMT‐related genes, CSCs markers, cell migration, invasion, sphere‐forming, and β‐catenin signaling pathway were explored. To evaluate the role of miR‐200c in anticancer effects by Zerumbone, miR‐200c was downregulated by LNA‐anti‐miR‐200c. Zerumbone significantly inhibited cell viability, migration, invasion, and sphere‐forming potential in HCT‐116 and SW‐48 cell lines. Zerumbone significantly suppressed the EMT and CSC properties as well as downregulated the β‐catenin. Silencing of miR200c reduced the inhibitory effects of Zerumbone on EMT and CSCs in CRC cells. These data indicated that Zerumbone may be a promising candidate for reducing the risk of CRC progression by suppressing the β‐catenin pathway via miR‐200c. - Journal of Cellular Physiology, Volume 233, Issue 12, Page 9538-9547, December 2018.