Scutellaria baicalensis (S. baicalensis) is a plant that is widely used for medicinal purposes. Baicalein, one of the primary bioactive compounds found in S. baicalensis, is thought to possess antitumor activity, although the specific mechanisms remain unclear. Therefore, the present study aimed to evaluate the ability of baicalein to disrupt the proliferation and metastatic potential of colorectal cancer (CRC) cells; a rapid and sensitive ultra-high performance liquid chromatography-tandem mass spectrometric method was employed for the identification of baicalein in an S. baicalensis aqueous extract and in rat plasma. To investigate the effects of baicalein, Cell Counting Kit-8 (CCK-8), western blotting, wound-healing and Transwell assays were performed. The data indicated that baicalein was absorbed into the blood and was able to effectively disrupt the proliferation, migration and invasion abilities of CRC cells in a dose- and time-dependent manner. Baicalein treatment was also revealed to decrease the expression of epithelial-mesenchymal transition (EMT)-promoting factors including vimentin, Twist1, and Snail, but to upregulate the expression of E-cadherin in CRC cells. The expression levels of cell cycle inhibitory proteins p53 and p21 also increased following baicalein treatment. In addition, Snail-induced vimentin and Twist1 upregulation, as well as E-cadherin downregulation, were reversed following treatment with baicalein. In conclusion, the results of the present study indicate that baicalein may suppress EMT, at least in part, by decreasing Snail activity.