Theranostic　nanoparticles　with　combined　imaging　and　therapy　functions　show　great　promise　in　cancer　precision　medicine.　In　this　study,　we　constructed　near-infrared　(NIR)　＂OFF-ON＂　fluorescent　nanohybrids　(F-PNDs)　for　synchronous　tumor　imaging　and　microRNA　(miRNA)　modulation　therapy　against　esophageal　cancer.　Nanodiamond　clusters　(NDs)　were　first　functionalized　for　protamine　sulfate　immobilization　(PNDs)　on　their　surfaces　via　a　noncovalent　self-assembling　approach　and　simultaneous　encapsulation　of　NIR　emitting　fluorescence　dye　cyanine　5　(Cy-5)　(F-PNDs).　Tumor　suppressor　miRNA-203　(miR-203)　was　then　adsorbed　onto　the　surface　of　F-PNDs　to　form　miR-203/F-PNDs　via　electrostatic　interactions.　The　size,　morphology,　photophysical　and　stability　properties　of　miR-203/F-PNDs　were　analyzed.　We　found　that　the　NIR　fluorescence　of　miR-203/F-PNDs　could　be　activated　to　the　＂ON＂　state　in　intracellular　environment　while　remaining　in　the　＂OFF＂　state　in　extracellular　or　blood　environment.　Furthermore,　in　vivo　live　imaging　experiments　showed　that　miR-203/F-PNDs　could　be　predominantly　accumulated　in　tumor　tissues　and　image　the　tumor　sites　24　h　postintravenous　injection.　In　addition,　intravenous　and　intratumoral　injection　of　miR-203/F-PNDs　could　efficiently　inhibit　tumor　growth　through　down-regulation　of　the　expressions　of　oncogenes　Ran　and　Delta　p63.　Our　study　indicated　that　miRNA/F-PNDs　could　serve　as　a　promising　theranostic　platform　for　synchronous　tumor　imaging　and　miRNA-based　modulation　therapy　against　cancer.