The anticancer effect of baicalein has been known for a number of years. However, its anti-metastatic effect and associated mechanisms in colorectal cancer (CRC) remain unclear. The present study investigated the hypothesis that treatment with baicalein may inhibit the proliferation, motility and invasion of human CRC cell lines via regulation of the protein kinase B (AKT) signaling pathway. Baicalein was demonstrated to significantly inhibit the migration and invasion of CRC cells (P=0.01). Additionally, after treatment with baicalein for 24 h, the protein expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 in CRC cells were significantly reduced in a dose-dependent manner (P=0.01). Furthermore, treatment with baicalein significantly reduced the expression levels of phosphorylated AKT (P=0.01). In conclusion, baicalein appears to inhibit CRC cell migration and invasion by reducing the expression of MMP-2 and MMP-9 via suppression of the AKT signaling pathway. Thus, baicalein is a potential novel therapeutic agent for patients with CRC.