The research of nanomaterials for bio-imaging and theranostic are very active nowadays with unprecedented advantages in nanomedicine. Homologous targeting and bio-imaging greatly improve the ability of targeted drug delivery and enhance active targeting and treatment ability of nanomedicine for the tumor. In this work, lycorine hydrochloride (LH) and magnetic iron oxide nanoparticles coated with a colorectal cancer (CRC) cell membrane (LH-FeO@M) were prepared, for homologous targeting, magnetic resonance imaging (MRI), and chemotherapy. Results showed that the LH-FeO@M and FeO@M intensity at HT29 tumor was significantly higher than that FeO@PEG, proving the superior selectivity of cancer cell membrane-camouflaged nanomedicine for homologous tumors and the MRI effect of darkening contrast enhancement were remarkable at HT29 tumor. The LH-FeO@M exhibited excellent chemotherapy effect in CRC models as well as LH alone and achieved a high tumor ablation rate but no damage to normal tissues and cells. Therefore, our biomimetic system achieved a homologous targeting, bio-imaging, and efficient therapeutic effect of CRC.