A new supramolecular nanocage, VMOP‐31, based on polyoxovanadate as the molecular building block, has been designed and synthesized under solvothermal conditions. The structure of VMOP‐31 was determined by single‐crystal and powder X‐ray diffraction, FTIR spectroscopy, UV/Vis spectrophotometry, and thermogravimetric analysis. The nanocage exhibits octahedral geometry and is constructed of six {V5O9Cl(COO)4} at the vertices and eight TATB (H3TATB=4,4′,4′′‐(s‐triazine‐2,4,6‐triyl)tribenzoic acid) ligands on the faces. Impressively, VMOP‐31 exhibited high efficiency in the inhibition of cell growth of solid tumors, such as human liver cancer cells SMMC‐7721, and superior results in the treatment of liver tumors in mice compared with classic cisplatin. Detailed studies revealed that the potential mechanism of cell death induced by VMOP‐31 involves cell cycle arrests, DNA damage, and subsequent apoptosis. Moreover, VMOP‐31 exhibited negligible side effects in the mice compared with cisplatin. To the best of our knowledge, VMOP‐31 is the first supramolecular nanocage applied to hepatic tumors both in vitro and in vivo. [ABSTRACT FROM AUTHOR]