Controlled drug delivery has demonstrated its great potential to alleviate the unpleasant side effects triggered by chemotherapeutic drugs through improving treatment efficacy in cancer cells while decreasing the adverse effects on normal cells. Herein, hexagonal MgAl-layered double hydroxide (Mg-Al LDH) nanoplates were fabricated by a facile hydrothermal strategy, which were developed as a promising pH-responsive drug delivery system for cancer treatment. The MgAl-LDH nanoplates possessed unique features including well-defined hexagonal morphology, uniform particle size, rough surface, typical mesoporous structure, and high specific surface area. The MgAl-LDH nanoplates exhibited a high drug loading capability of 0.36 mg/mg using non-anionic doxorubicin hydrochloride (DOX) as a classical anticancer model drug. The loaded DOX displayed a sustained and pH-controlled release characteristic with sufficient release of 91.4% and 69.9% under acidic pH values (4.0, 5.5) and suppressed release of 37.8% at a neutral pH level (7.4) after 48 h of release. Furthermore, the developed MgAl-LDH nanoplates displayed good biocompatibility without any obvious cytotoxicity to human breast cancer cells (MCF-7), and DOX-loaded MgAl-LDH exerted the effects of significant suppression of cell proliferation and induction of apoptosis in regions of high concentration.