Herein, a pH-responsive dual cross-linked hydrogel for controlled drug release is presented. The hydrogel was constructed with reversible borate ester bonds and crystalline poly(vinyl alcohol). By changing the environmental pH, its physicochemical characteristics, including rheological properties, mechanical properties, microstructural features, and the biocompatibility of the gels, were evaluated. The gels at tumor acidic conditions exhibited swelling and lower compressive strength and modulus than those in a physiological environment, which was attributed to the pH-responsive borate ester bonds and the protonation of amine groups on the PEI polyelectrolyte. Importantly, the drug-encapsulated biocompatible hydrogel showed sustained and increased release under an acidic environment, and it followed the Fickian diffusion mechanism. Therefore, it exemplifies that borate ester bond-based pH-responsive biomaterials have high promise in biomedical research, especially for drug delivery.