In this paper, a novel halloysite-based hydrogel with a "turn-on" fluorescence character upon H2O2 was facilely prepared and used to construct the H2O2-responsive drug delivery system, in which a coprecipitation method was proposed to afford the drug-loaded halloysite nanotubes (DHNTs). DHNTs were carefully characterized by FTIR, TGA, XPS, XRD and TEM to demonstrate that the drugs were mainly loaded into the cavity rather than attached on the external surface of halloysite nanotubes (HNTs). The B-C linkage in the as-prepared hydrogel was broken in the presence of H2O2, resulting in the degradation and thereby a responsive release. The drug release was almost not occurred under the physiological concentration ([H2O2] = 0.02 mu M), while a complete release ( > 90%) can be achieved under pathological concentration ([H2O2] = 200 mu M). Moreover, the broken of B-C linkage triggered a transformation from arylboronates to phenols, in which the formed fluorescein gave rise to the change from non-fluorescent to fluorescent of the hydrogels. The fluorescence intensity enhanced with the increase of release rate, in which a good linear relationship can be achieved. The attractive properties make the halloysite-based hydrogels a promising application in the field of biomedicine.