Surface modification of nanoparticles with cellular protein components is a new biomimetic modification strategy, which utilizes the inherent affinity between homologous cells to introduce the same surface molecules into nanoparticles to improve the targeting performance. In this study, oleic acid (OA)-coated Fe3O4 nanocubes were prepared by a high-temperature thermal decomposition method and modified by 3, 4-dihydroxyphenylpropionic acid (DHCA); then, HeLa cell membranes were introduced onto the surface of the nanocubes through mixed coextrusion to try to endow them with the targeting function of natural cells. The results show that the prepared Fe3O4 nanocubes have high monodispersity, excellent water solubility, and biocompatibility. Moreover, the Fe3O4 nanocubes encapsulated by cellular protein show an obvious core-shell structure and the specific targeting property to HeLa cells is improved significantly, which is expected to be used in clinical targeted diagnosis and treatment of cancer.