Abstract: Podoplanin(PDPN), a type-Ⅰtransmembrane glycoprotein, was expressed in a variety of human tumor cells. C-type lectin-like receptor 2 (CLEC-2) is a type-Ⅱ transmembrane glycoprotein. It is a novel receptor for podoplanin, expresses on the surface of platelet and induces platelet activation by interacting with PDPN. Aggregated platelets coat tumor cells during their transit through the bloodstream and mediate adherence to vascular endothelium, evasion from immune molecules, and release of an array of bioactive molecules that facilitate tumor cell extravasation and growth at metastatic sites. It suggests that PDPN and CLEC-2 are promising targets for developing new therapies against cancer metastasis. This review will focus on the mechanisms of PDPN and CLEC-2 in tumor metastasis, summarize and outlook the recent progress of treatment.