Background:　Highly　Active　Metastasis　Preventing　Therapy　(HAMPT)　is　a　quardruple　drug　combination　consisting　of　mifepristone,　aspirin,　lysine　and　doxycycline.　Objective:　Based　on　our　previous　study,　here,　we　further　proved　that　HAMPT　could　effectively　and　safely　prevent　colon　cancer　metastasis.　Methods:　It　was　specifically　designed　for　synergistically　controlling　key　cancer　metastatic　pathways.　The　dose　of　HAMPT　was　designed　at　lower　than　the　pharmaceutically-recommended　dose,　and　thus　the　sub-healthy　cancer　survivors　may　take　HAMPT　safely　and　for　a　long　time　for　metastasis　chemoprevention.　Results:　HAMPT　within　its　effective　concentration　range　(1-50　μg/mL)　showed　no　cytotoxicity　to　colon　cancer　cells　HT-29　and　CT-26,　but　significantly　inhibited　adhesion　and　invasion　of　these　colon　cancer　cell　lines　to　human　umbilical　vascular　endothelial　cells　(HUVECs),　and　to　Matrigel.　HAMPT　exhibits　a　good　adhesion　inhibited　ratio,　suggesting　that　it　functions　primarily　by　inhibiting　adhesion　of　the　cancer　cells　to　HUVECs,　rather　than　killing　the　cancer　cells.　At　low　concentrations,　HAMPT　also　inhibited　cancer　cell　migration.　Flow　cytometry　analysis　revealed　that　HAMPT　had　no　significant　effect　on　cell　cycle,　but　inhibited　IL-1β-induced　expression　of　both　E-selectin　of　HU-VECs　and　Sialyl-Lewis　X　of　HT-29.　The　in　vivo　experiment　showed　that　HAMPT　suppressed　metastasis　of　CT-26　cells　to　mouse　lungs　in　a　dose-dependent　manner.　In　the　mouse　model,　HAMPT　showed　advantages　in　preventing　metastasis　over　other　combinations.　Conclusion:　The　present　study　demonstrated　that　HAMPT　is　a　novel　quadruple　drug　combination　that　can　safely　and　effectively　prevent　cancer　metastasis.　©　2019　Bentham　Science　Publishers.