Efficient　energy　transfer　is　a　promising　strategy　in　overcoming　the　inherent　limits　of　a　narrow　band　and　weak　absorption　of　lanthanide　ions　due　to　the　nature　of　4f-4f　transitions.　Herein,　we　introduce　a　nanoparticle-sensitized　nanoparticle　system　where　a　near-infrared-emitting　quantum　dot　(QD)　is　used　as　a　sensitizer　with　broadband　photon　absorption　for　a　lanthanide-doped　nanoparticle　(LNP)　to　generate　second　near-infrared　(NIR-II)　emission.　The　NIR-II　luminescence　of　Er3+-doped　LNP　by　Ag2S　QD　sensitization　displays　an　enhancement　of　∼17-fold　in　intensity　and　∼10-fold　in　brightness　over　bare　LNP　because　of　increased　absorptivity　and　overall　broadening　of　the　absorption　spectrum　of　LNP.　Furthermore,　a　QD-sensitized　LNP　system　exhibits　excellent　photostability　and　is　able　to　improve　the　signal-to-noise　ratio　of　tumor　NIR-II　imaging　via　in　situ　cross-linking　of　QD　and　LNP.　The　QD-sensitized　LNP　system　for　luminescence　enhancement　opens　a　potential　avenue　for　efficient　energy　transfer　in　complex　nanoparticle-nanoparticle　systems.　©　2020　American　Chemical　Society.