Colorectal cancer remains as a serious global cause of morbidity and mortality. The current therapies for colorectal cancer treatment are still unsatisfactory and thus, identification of novel targets is an urgent requisite. Recent evidence has reported miRNAs are closely correlated with colorectal cancer development. miR-150 has been identified in tumor progression in various cancers. Nevertheless, its roles in colorectal cancer remain poorly known. In our study, a decreased miR-150 expression in colorectal cancer tissues and cells was observed. Meanwhile, we reported a negative correlation between miR-150 and β-catenin in colorectal cancer. β-catenin can participate in the physiological mechanism of many types of cancers. Then, miR-150 was overexpression in SW480 and HT-29 cells and it was show that miR-150 repressed SW480 and HT-29 cell viability, proliferation and colony formation capacity. Moreover, colorectal cancer cell progression was triggered by the inhibition of miR-150 via negatively regulating β-catenin. Subsequently, the direct binding correlation between miR-150 and β-catenin was demonstrated. β-catenin, c-myc and CyclinD1 level was significantly restrained by the up-regulation of miR-150 in SW480 and HT-29 cells. Finally, it was proved that miR-150 depressed colorectal cancer growth through modulating β-catenin in vivo. Overall, it was implied that miR-150 could inhibit colorectal cancer progression and serve as a tumor suppressor via inactivating β-catenin pathway.