Monodisperse poly(acrylic acid)-modified Fe3O4 (PAA@Fe3O4) hybrid microspheres with dual responses (magnetic field and pH) were successfully fabricated. The PAA polymer was encapsulated into the inner cavity of Fe3O4 hollow spheres by a vacuum-casting route and photo-initiated polymerization. TEM images show that the samples consist of monodisperse porous spheres with a diameter around 200 nm. The Fe3O4 spheres, after modification with the PAA polymer, still possess enough space to hold guest molecules. We selected doxorubicin (DOX) as a model drug to investigate the drug loading and release behavior of as-prepared composites. The release of DOX molecules was strongly dependent on the pH value due to the unique property of PAA. The HeLa cell-uptake process of DOX-loaded PAA@Fe3O4 was observed by confocal laser scanning microscopy (CLSM). After being incubated with HeLa cells under magnet magnetically guided conditions, the cytotoxtic effects of DOX-loaded PAA@Fe3O4 increased. These results indicate that pH-responsive magnetic PAA@Fe3O4 spheres have the potential to be used as anticancer drug carriers.