This study aimed to investigate the effect of baicalein on migration and invasion of human cutaneous squamous cell carcinoma A431 cells. A431 cells were incubated with baicalein with concentrations of 0 (control), 2, 4, 8, 16 and 32 mu mol/L, respectively. The cell proliferation, apoptosis, migration, invasion and expressions of matrix metalloproteinse-2 (MMP-2), matrix metalloproteinse-9 (MMP-9) and vascular endothelial growth factor (VEGF) protein were detected. Results showed that, with 32 mu mol/L baicalein and treatment for 72 h, the cell proliferation inhibition and apoptosis rates were the highest. With 32 mu mol/L baicalein and treatment for 48 h, the cell migration and invasion inhibition rates were the highest, and the MMP-2, MMP-9 and VEGF protein expression levels were the lowest. In conclusion, baicalein can inhibit the proliferation of A431 cells, promote the apoptosis, and inhibit the invasion and metastasis. The mechanism may be related to its down-regulation of MMP-2, MMP-9 and VEGF expressions.