Backgrounds: Coix lachryma-jobi L. var. ma-yuen Stapf which is the native plant of Southeast Asia, exists in the wild and is also cultivated. Although this plant has used as a diuretic, stomachic, analgesic, arthritis and antispasmodic agent, and could reduce liver fat accumulation and protect cells from the tumor stimulating compounds, the anti-cancer effect of Coix sprout extract (CSE) is unknown. Therefore, we elucidated whether CSE has anti-cancer effect in colon cancer cells. Methods: To evaluate the effect of CSE on the cell growth, cell cycle, and signal pathways, we performed MTT assay, flow cytometry analysis, and Western blot analysis in HCT116 cells. Furthermore, scratched wound healing, transwell migration, and invasion assays were conducted to monitor whether CSE regulates migration and invasion of colon cancer cells under hypoxia. Results: CSE inhibited the growth of HCT116 cells in 0.75, 1 mg/mL concentrations for 24 h, and resulted in G2/M phase arrest. Moreover, we examined whether CSE has anti-metastatic effect under hypoxia in colon cancer cells. CSE decreased DFO-induced motility of colon cancer cells by 77.4%, and blocked migration of colon cancer cell by 73.9% compared to hypoxia control group. Finally, CSE inhibited 43% of hypoxia-induced invasiveness of colon cancer cells through suppressing activation of ERK1/2 and Akt pathways. Conclusions: CSE inhibits migration and invasion of colon cancer cells via repressing ERK1/2 and Akt pathways. Keywords: Coix sprout extract, Colon cancer, metastasis, invasion