Thrombosis　is　a　frequent　predisposing　factor　in　high-mortality　cardiovascular　diseases,　which　underscores　the　urgent　need　to　precisely　diagnose　thrombosis　formation　at　a　less　severe　stage.　However,　it　is　still　challenging　to　realize　in　vivo　early　thrombosis　imaging　due　to　lack　of　high　sensitivity/-specificity　molecular　imaging　strategy.　To　address　such　problems,　thrombin-activatable　scintillating　nanoprobes　are　developed　for　background-free　X-ray-excited　luminescence　(XEL)　imaging　of　in　vivo　early　thrombosis.　The　nanoprobes　are　constructed　by　designing　bright　XEL-emitting　lanthanide-doped　scintillator　nanocrystals　(NCs)　with　dye　labeled-peptide　modification.　Such　nanoprobes　show　XEL-off　originally　and　enable　robust　turn-on　XEL　upon　thrombin-specific　cleavage　of　the　peptide,　resulting　from　the　rational　manipulation　of　energy　transfer　between　dye　and　NCs.　Specially,　due　to　high　tissue　penetration　depth　and　background-free　attributes　in　XEL　imaging,　this　strategy　achieves　high-efficiency　XEL　imaging　of　the　early　thrombosis　on　the　basis　of　in　situ　elevated　thrombin　levels.　Moreover,　XEL　and　magnetic　resonance　imaging　capabilities　can　be　integrated　to　further　improve　imaging　accuracy　and　monitor　thrombosis　progression.　As　such,　the　exploited　strategy　demonstrates　a　novel　paradigm　for　realizing　timely　thrombosis　imaging　and　provides　a　new　readily　tailorable　platform　for　sensitive　in　vivo　deep-tissue　imaging.　©　2020　Wiley-VCH　GmbH