In this paper, a novel pH-responsive drug delivery system based on hierarchical hollow mesoporous MnFe 2 O 4 nanospheres was developed for potential application in cancer treatment. The well-defined hollow mesoporous MnFe 2 O 4 nanospheres were directly fabricated via a facile one-step solvothermal approach without the involvement of additional templates. A mechanism of inside-out Ostwald ripening was suggested to account for the formation of hollow mesoporous nanostructures. The morphology, crystal structure, chemical composition, magnetic properties, thermal stability and mesoporous characteristics of the fabricated MnFe 2 O 4 nanospheres were comprehensively assessed based on various analysis techniques. The resulting hollow mesoporous MnFe 2 O 4 nanospheres with a high biocompatibility were able to be served as a nanocarrier for loading and delivering of anticancer drug doxorubicin (DOX). In vitro drug release study revealed that DOX release from DOX-loaded MnFe 2 O 4 nanospheres was significantly restrained in pH 7.4 phosphate buffer solution (PBS), while it was markedly accelerated in pH 4.5 PBS. The results of cytotoxicity assay and inverted biological microscopy demonstrated that the DOX-loaded MnFe 2 O 4 nanospheres were more cytotoxic against HepG2 cells than MnFe 2 O 4 nanospheres due to the evident inhibition effect of released DOX from the constructed drug delivery system. Therefore, the developed pH-responsive delivery system will have a great potential for its practical application in cancer treatment. [Display omitted] • Hollow mesoporous MnFe 2 O 4 nanospheres were prepared by a facile template-free solvothermal method. • An inside-out Ostwald ripening mechanism was proposed for the formation of hollow structures. • Typical superparamagnetic behavior with saturation magnetization of 69.1 emu/g. • In vitro negligible cytotoxicity was observed even at high sample concentrations. • A promising drug delivery system with high drug loading capacity and pH-responsive release ability. [ABSTRACT FROM AUTHOR]