Luteolin, 3',4',5,7-tetrahydroxyflavone, a natural flavonoid component found in various Chinese herbs such as Scutellaria barbata D. Don, honeysuckle, chrysanthemum, schizonepeta, and ajuga decumbens, exhibits potential for cancer prevention and therapy. This study elucidates the molecular mechanisms by which luteolin, an active constituent of Scutellaria barbata, inhibits invasion and metastasis of hepatocellular carcinoma (HCC) cell lines both in vitro and in vivo. The oncogenic microRNA miR-6809-5p was found to be aberrantly upregulated in HCC tissues and downregulated by luteolin in HCC cells; overexpression of miR-6809-5p was able to restore the anti-HCC effects of luteolin via the miR-6809-5p/FLOT1/FAK signaling pathway. Furthermore, luteolin suppressed HCC invasion, metastasis, and epithelial-mesenchymal transition (EMT) through modulation of the PI3K/AKT/mTOR pathway, affecting markers such as E-cadherin, β-catenin, Vimentin, N-cadherin, Snail, Twist, and Slug. This research demonstrates that luteolin effectively inhibits HCC cell migration and invasion and significantly suppresses epithelial mesenchymal transition (EMT) both in vitro and in vivo.