Metastasis　is　the　primary　cause　of　cancer　recurrence　and　cancer　related　mortality　in　triple-negative　breast　cancer　(TNBC).　EGFR　overexpression　is　in　50-75%　TNBC　and　EGFR-mediated　signaling　has　potential　as　an　attractive　therapeutic　target　in　some　specific　subtypes　of　breast　cancer　due　to　its　significant　association　with　tumor　metastasis　and　poor　prognosis.　Therefore,　identification　of　promising　therapeutic　strategies　targeting　EGFR　with　higher　specificity　toward　cancer　metastasis　is　urgently　needed.　20(S)-protopanaxadiol　(PPD),　one　of　the　major　active　metabolites　from　Panty(　ginseng,　has　been　widely　reported　to　possess　pleiotropic　anticancer　activities　in　various　cancers.　In　this　study,　we　investigated　the　effect　of　PPD　against　cancer　metastasis　and　the　related　molecular　mechanisms　in　TNBC　in　vitro　and　in　vivo.　PPD　(　＞　30　mu　M)　suppressed　cell　proliferation　by　arresting　cell　cycle　in　G0/1　phase　and　triggering　cells　apoptosis　as　shown　by　cell　viability　assay,　flow　cytometry　analysis　and　colony　formation　assay,　whereas　lower　dose　of　PPD　(＜　20　mu　M)　decreased　metastatic　potential　of　MDA-MB-231　and　SUM159　cells　through　direct　inhibition　of　cell　adhesion,　motility　and　invasiveness.　In　TNBC　xenograft　and　syngeneic　models,　PPD　treatment　markedly　decreased　tumor　growth　and　lung　metastasis.　PPD　reversed　epithelial-mesenchymal　transition　(EMT),　decreased　the　expression　and　activity　of　matrix　metalloproteinases　(MMPs)　while　increased　the　expression　of　tissue　inhibitors　of　metalloproteinases　(TIMPs)　as　shown　by　Western　blot　and　gelatin　zymography.　Cell　signaling　pathways　that　control　the　expression　or　activation　of　these　processes　were　investigated　by　Western　blot　and　ELISA　assay.　PPD　treatment　reduced　the　phosphorylation　of　EGFR　and　down-regulated　the　activation　ERK1/2,　p38　and　JNK　signaling,　which　was　further　validated　by　using　the　agonists　or　inhibitors　of　EGFR　and　MAP　kinases　family.　Collectively,　these　findings　suggest　that　PPD　holds　therapeutic　potential　against　the　tumor　metastasis　of　TNBC　via　targeting　EGFR-mediated　MAPK　pathway.