High　hydrogen　sulfide　(H2S)　expression　has　been　shown　to　play　a　crucial　role　in　tumor　growth　and　proliferation　in　colon　cancer.　So　far,　most　probes　used　for　monitoring　H2S　offer　single-modal　imaging,　which　makes　the　collection　of　accurate　information　for　tumor　diagnosis　difficult.　In　the　present　study,　a　novel　dual-modal　imaging　probe　in　the　second　near-infrared　(NIR-II,　950-1700)　window　is　proposed　and　constructed　by　coating　a　uniform　shell　of　polydopamine　(PDA)　on　the　surface　of　cuprous　oxide　(Cu2O)-conjugated　downconversion　nanoparticles　(DCNPs).　Of　note,　DCNP-Cu2O@PDA　is　in　the　“on”　state,　with　emission　centered　at　1550 nm　(irradiation　using　a　980nm　laser)　in　non-neoplastic　tissues.　Colon　tumors　with　endogenous　H2S　overexpression　can　induce　the　in　situ　transformation　of　Cu2O　to　copper　sulfide　(Cu2-XS）.　Owing　to　the　competitive　absorption　between　Cu2-XS　and　DCNPs　at　a　wavelength　of　980 nm,　the　generated　DCNP-Cu2-XS@PDA　exhibits　a　quenched　NIR-II　fluorescence　(FL)　signal.　Meanwhile,　Cu2-XS　exhibits　a　strong　absorbance　at　1250 nm,　enhancing　the　NIR-II　photoacoustic　(PA)　signal　accompanied　by　NIR-II　FL　attenuation.　The　switching　in　PA　and　FL　signals　at　the　tumor　site　offered　“double　assurances”　for　the　accurate　monitoring　of　H2S.　©　2023　Wiley-VCH　GmbH.