A new ratiometric fluorescent H2O2 probe, benzopyrylium-coumarin (BC), is designed by using an oxonium moiety as the unique H2O2 response site. The BC probe exhibits an extremely large emission shift of 221 nm in response to H2O2, and is successfully applied for the simultaneous near-infrared and two-photon imaging of H2O2 in living cells, mouse-liver tissues, and zebrafish. [GRAPHICS] .