We present the formation of the largest titanium-oxo cluster, [Ti42(μ3-O)60(OiPr)42(OH)12)](6-), with the first fullerene-like Ti-O shell structure. The {Ti42O60} core of this compound exemplifies the same icosahedral (Ih) symmetry as C60, the highest possible symmetry for molecules. According to the coordination environments, the Ti centers in this cluster can be arranged into a Platonic {Ti12} icosahedron and an Archimedean {Ti30} icosidodecahedron. The solution stability of this cluster was confirmed by electrospray ionization mass spectrometry. The spherical body of the {Ti42O60} core has an inside diameter of 1.05 nm and an outside diameter of 1.53 nm, which could be directly visualized by high-resolution transmission electron microscopy. Our results demonstrate that titanium oxide can also form fullerene-like shell structures.