AbstractIdentification of cancer from normal tissues is important for early diagnosis of cancer. Combined detection of multiple tumor markers is important for accurate diagnosis. It is urgent to develop fluorescent probes that are responsive to multiple cancer characterizations for selective cancer imaging. Herein, we designed a novel near‐infrared (NIR) fluorescent probe (IRAPA) using a hemi‐cyanine skeleton as fluorophore and 3‐acrylamidopropanoic ester as recognizing unit that is responsive to both oxidative and reductive molecules. IRAPA has faint fluorescence emission as the intramolecular charge transfer (ICT) process is blocked. H2O2, glutathione (GSH) and cysteine (Cys) can individually induce the hydrolysis of ester bond and give fluorescent NIR IROH. IRAPA shows low cytotoxicity and produces strong fluorescence specifically in cancer cells/tissues. While the normal cells/tissues showed very weak fluorescence. Moreover, IRAPA shows higher differences between cancer and normal cells compared to probes that only response to biothiols or ROS.