Agents enabling tumor staging are valuable for cancer surgery.Herein a targetable sialic acid‐armed near‐infrared profluorophore(Sia‐pNIR)is reported for fluorescence guided tumor detection.Sia‐pNIR consists of a sialic acid entity effective for in vivo tumor‐targeting and a proflurophore which undergoes lysosomal acidity triggered fluorogenic isomerization.Sia‐pNIR displays a number of advantageous biomedical properties in mice,e.g.high tumor‐to‐normal tissue signal contrast,long‐term retention in tumor and low systemic toxicity.In addition,Sia‐pNIR effectively converts NIR light into cytotoxic heat in cells,suggesting tumor‐activatable photothermal therapy.With the high performance tumor illumination and lysosome‐activatable photothermal property,Sia‐pNIR is a promising agent for detection and photothermal ablation of surgically exposed tumors.