Inorganic halloysite nanotube (HNT) was modified with organic fluorescein derivative (PA) to prepare HNTs-based hybrid fluorescence probe (HNTs-PA). Thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), solid-state 13C NMR spectroscopy, X-ray photoelectron spectroscopy (XPS), energy dispersive spectrum (EDS) and transmission electron microscopy (TEM) confirmed that PA was successfully grafted onto the lumen of HNTs to give HNTs-PA with a grafting degree of 6.0%. The established B-C bond endows a selective fluorescent response upon hydrogen peroxide (H2O2) to HNTs-PA. The fluorescence of the new hybrid probe exhibits a highly specific “turn-on” response to H2O2 over other reactive oxygen species (ROS) and common ions owing to their chemoselective boronate-to-phenol switch. The “turn-on” response can even be tracked when the additional amount of H2O2 was limited to 1 × 10?7 mol. Moreover, human lung cancer cells (A549 cells) can be successfully stained and the staining intensity enhanced as time prolongs, which can be owing to the overexpressed H2O2 of cancer cells. Thus, the as-prepared organic?inorganic hybrid fluorescence probe may open up a broader application for identification and diagnosis.