Herein, a kind of dual acid-sensitive nanoparticles based on monomethoxy poly(ethylene glycol)-imine-β-cyclodextrin is constructed by a facile phenylboronic acid-cross-linked way. The data of dynamic light scattering and transmission electron microscope reveal the cross-linked nanoparticles have improved stability. The cross-linked nanoparticles could easily self-assemble and load the anticancer drug at neutral pH condition. However, when the drug-loaded nanoparticles are delivered to extracellular tumor sites (pH ≈6.8), the surface of the nanoparticles would be amino positively charged and easily internalized by tumor cell due to the cleavage of the acid-labile benzoic-imine. Subsequently, with the acidity in subcellular compartments significantly increasing (such as the endosome pH ≈5.3), the loaded drug would fast release from the endocytosis carriers due to the hydrolysis of boronate ester. These features suggest that these dual acid-sensitive cross-linked nanoparticles not only possess excellent biocompatibility but also can efficiently load and deliver anticancer drug into tumor cells to enhance the inhibition of cellular proliferation, outlining a favorable platform as drug carriers.