The synthesis of H 2 O 2 -activatable small molecules in the second near-infrared (NIR-II) window remains challenging. We present the NIR-II probe Z-1065 for real-time detection of H 2 O 2 . Z-1065 demonstrates high sensitivity and selectivity towards H 2 O 2 in vitro and effectively monitors H 2 O 2 generation in drug-induced liver injury (DILI) mouse models.