Oridonin (Ori) is a natural active component with superior anticancer properties; however, its clinical application is severely limited by the inherent properties of short half‐life, limited bioavailability, and low water solubility. Some metal–organic frameworks (MOFs) materials have unique porous structure and appropriate nanometer particle size that are attractive in drug delivery. Herein, a folic acid (FA)‐functionalized Fe‐MOF was designed to efficiently incorporate Ori for targeting delivery to cancer cells and improve anticancer effects. The synthesized Fe‐MOF‐FA@Ori showed an average particle size of 200 nm with a loading capacity of 12.57%. The cytotoxicity assay confirmed that Fe‐MOF‐FA@Ori was effective in inhibiting the proliferation of SMMC‐7721 cells. Mechanistically, the synthesized nanoparticle induced apoptosis and blocked the progression of the G0/G1 phase cell cycle on SMMC‐7721 cells. Cell metastasis and invasion assays demonstrated that Fe‐MOF‐FA@Ori had good anti‐metastatic ability against SMMC‐7721 cells. Overall, Fe‐MOF‐FA is a potent drug carrier for targeting cancer therapy.