Rare　circulating　tumor　cells　(CTCs)　cause　＞50%　of　primary　colorectal　cancer　survivors　to　develop　deadly　metastasis　at　3-5　years　after　surgery;　the　current　chemotherapies　can　do　nothing　about　these　cells.　Herein,　we　synthesized　a　novel　doxorubicin　(DOX)-entrapped　mesoporous　silica　nanoparticle　(MSN),　covalently-conjugated　with　two　aptamers,　for　simultaneously　targeting　EpCAM　and　CD44,　the　typical　surface　biomarkers　of　colorectal　CTCs.　The　nanomissile　can　specifically　capture　the　metastasis-prone　CTCs　spiked　in　healthy　human　blood　in　a　competitive-binding　manner.　The　binding　not　only　accurately　delivers　DOX　into　the　cancer　cells　via　the　biomarker-mediated　endocytosis　to　inhibit　CTC　viability　through　the　DOX-dependent　mechanism,　but　also　inhibits　the　adhesion　of　cancer　cells　to　the　endothelium　and　the　consequent　transmembrane　migration　through　the　DOX-independent　mechanism.　The　molecular　entity　of　the　conjugate　and　its　pharmaceutical　DOX　encapsulation-releasing　capacity　are　well-demonstrated　via　various　physiochemical　characterizations　including　gel　electrophoresis,　which　proves　the　＞8-hour　biostability　of　the　nanomissile　in　blood,　long　enough　for　it　to　chase　CTCs　in　mice　and　synergistically　inhibit　the　CTC-induced　lung　metastasis　more　potently　than　its　single　aptamer-conjugated　counterparts　and　DOX　itself.　The　present　strategy　may　pave　a　new　avenue　for　safe　and　effective　cancer　metastasis　chemoprevention.　©　The　Royal　Society　of　Chemistry　2017.