Solasodine is a naturally occurring aglycone of glycoalkaloid in a number of Solanumspecies (Solanaceae). Solasodine is used for the production of steroid drug in medical industryand that have been reported to inhibit proliferation in various tumor cells. However, the effectof solasodine on tumor metastasis remains unclear. This study investigates the suppressionmechanism of solasodine on motility of human lung cancer cell A549 in vitro. Results showthat solasodine inhibits viability of lung A549 cells in a dose-dependent manner. When treatedwith non-toxic doses of solasodine, cells invasion were suppressed significantiy by in vitroBoyden chamber invasion assay. Solasodine reduces the mRNA level of matrixmetalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix metalloproteinase(EMMPRIN), but increases the expression of reversion-inducing cysteine-rich protein withkazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2.Immunoblotting assays indicate that solasodine is effective in suppressing Aktphosphorylation. Moreover, solasodine downregulates oncogenic microRNA-21 (miR-21),which has been known to target RECK. Downregulation of miR-21 by miR-21 inhibitorincreases RECK expression and decreases cell invasion, suggesting that downregulation ofmiR-21 by solasodine may contribute to elevate RECK expression and subsequentlyinhibiting cell invasion. Taken together, the results reveal that inhibition of A549 cell invasionby solasodine may be, at least in part, through blocking MMP expression. Solasodine alsoreduces PI3K/Akt signaling pathways and downregulates exression of miR-21. These findingsdemonstrate an attractive therapeutic potential for solasodine in anti-metastatic therapy.