Great photoelectric properties can herald the high potentials of CsPbBr₃ nanocrystals (NCs) to function as the fluorescent probes for early tumor diagnosis. However, the intrinsic water vulnerability of CsPbBr₃ NCs highly restricts their biomedical applications. To conquer this challenge, we herein introduce a nature inspired "stress-response" method to tightly encapsulate CsPbBr₃ into SiO₂ nano-shells that can dramatically improve the water stability of CsPbBr₃@SiO₂ nanoparticles for over 48 h. We further highlighted the advantageous features of CsPbBr₃@SiO₂ by using them as the fluorescent probes for CT26 tumor cell imaging with their high water stability, biocompatibility, and low cytotoxicity. Our work for the first time exhibited the potential of lead halide perovskite NCs for tumor diagnosis, and can highly anticipate the further in vivo biomedical applications that light up live cells.