An Atg4B-responsive peptideAc-Thr-Phe-Gly-d-Cys (TFGC) and a cathepsin B-activatablecompound Ac-Lys-Gly-Arg-Arg-CBT (KGRR-CBT) were rationally designed.During tumor autophagy, these two compounds were uptaken by cancercells and cleaved by their corresponding enzymes to yield d-cysteine and 2-cyano-6-aminobenzothiazole, respectively, which underwenta CBT-Cys click reaction to yield d-aminoluciferin, turningthe bioluminescence “on”. Here, CTSB is linked to neoplasm.