Surface-Enhanced Raman Spectroscopy attracts great interests for its ability to detect a variety of molecules at trace level. However, the commonly used noble metal substrates suffer from high cost, poor biocompatibility and inferior stability. Some oxides have the potential to substitute for noble metal and much effort has been made to improve their performance. In this paper, MoO₂ nanocones were prepared and self-assembled into hollow spheres. The structure exhibits an enhancement factor (EF) of 3 × 10⁷ and a limit of detection (LOD) of 10⁻⁹ M for Rhodamine 6G (R6G). This performance is among the best of all the oxides and is comparable to that of Au and Ag. The morphology control of hollow MoO₂ sphere was also discussed.