SFN, including its two isomers of R-SFN and S-SFN, significantly inhibited TGF-1-induced migration and invasion in MDA-MB-231 cells. Proteomic and phosphoproteomic analysis showed that SFN affected the formation of cytoskeleton. Subsequent experiments confirmed that SFN significantly inhibited TGF-1-induced actin stress fiber formation and the expression of actin stress fiber formation-associated proteins, including paxillin, IQGAP1, FAK, PAK2, and ROCK.