Drug-induced hepatotoxicity is a long-standing concern of modern medicine. The production of peroxynitrite (ONOO) is proposed as an early sign of the progression of drug-induced hepatotoxicity. However, conventional blood tests fail to offer a real-time unambiguous visualization of such hepatotoxicity . ONOO probes that are currently reported are mainly located in the visible or the first near-infrared (NIR-I) window, which have limited biosensing application due to the autofluorescence and photon scattering. Here, we report an ONOO responsive cyanine dye, IR-1061 -aggregate ( ), which exhibits a red shift over 500 nm, with an absorption peak at 1580 nm in the NIR-IIb region. By conjugating with rare earth nanoparticles (RENPs) that have NIR-IIb emission at 1550 nm, a dual-mode imaging probe RENPs- is developed. RENPs- shows a fast and sensitive response to ONOO, with activatable NIR-IIb fluorescence and a change in the photoacoustic signals, which is successfully applied for real-time monitoring of hepatotoxicity .