Baicalein, one of the major flavonoids in Scutellaria baicalensis, has been used in anti-inflammatory and anticancer therapies for a long time. However, the antimetastatic effects and related mechanism(s) in gastric cancer remain unclear. In the present study, we tested the hypothesis that administration of baicalein may inhibit the proliferation, motility and invasion of human gastric cancer cell lines by regulating the p38 signaling pathway. In the present study, we found that baicalein could inhibit migration and invasion of gastric cancer cells. Additionally, after treating with baicalein for 24 h, the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in gastric cancer cells were reduced in a dose-dependent manner. Moreover, baicalein clearly reduced the phosphorylated levels of p38. Combined treatment with p38 activator partially blocked the antimetastatic effects of baicalein, while p38 inhibitor (SB203580) and baicalein resulted in a synergistic reduction in MMP-2 and -9 expression; the invasive ability of gastric cancer cells was also inhibited. In conclusion, baicalein inhibits gastric cancer cell invasion and metastasis by reducing cell motility and migration via suppression of the p38 signaling pathway, suggesting that baicalein is a potential therapeutic agent for gastric cancer.