Uniform hollow magnetic supraparticles (HMSPs) consisting of nanocrystal aggregates in shells are designed and fabricated via a one-pot microwave irradiation process within 10 min, employing casein, a major milk protein, as a structure-directing agent responsible for the formation of hollow structures. The casein micelle (CM)-mediated self-assembled HMSPs exhibit structural uniformity, excellent aqueous dispersibility, enhanced biocompatibility, as well as a high saturation magnetization (∼70 emu g-1). Herein, CMs serve as soft templates to induce inner hollow cavities through electrostatic interactions between negative CM "brushes" and positive Fe(iii) species, and subsequent degradation of the inner cores under microwave irradiation, meanwhile improving the colloidal stability and biocompatibility of the HMSPs. Besides, the interior cavity size of the HMSPs could be readily tuned in the range of 40 nm to 150 nm, simply by varying the feeding dosage of casein. In light of the interior void and desirable physicochemical properties, the role of HMSPs serving as vehicles for the controlled delivery of DOX into cancer cells has been investigated. Drug release profiles are shown to be pH-responsive with up to 83% DOX release in acidic environments (pH 4.0 and 5.0), whereas low DOX (18%) release occurs at neutral pH (pH 7.4) within 48 h, indicating minimal premature drug release. Moreover, intracellular tracking experiments reveal that DOX-loaded HMSPs could efficiently be taken up by KB cells and exhibit potent anti-proliferation and inhibitory effects against KB cells, as compared to free DOX. Importantly, the DOX-loaded HMSPs show limited cytotoxicity against normal HEK 293 cells with 70% retained viability after incubation at a high concentration of 5.0 μg mL-1, which further demonstrated the potential of microwave-driven HMSPs as desirable drug delivery vehicles.