Toluene is the most common volatile organic compound (VOC), and the MnO 2 -based catalyst is one of the excellent nonprecious metal catalysts for toluene oxidation. In this study, the effects of MnO 2 precursors and the support types on the oxidation performance of toluene were systematically explored. The results showed that the 15MnO 2 /MS-CeO 2 -N catalyst with Mn(NO 3 ) 2 ·4H 2 O as the precursor and the mesoporous CeO 2 nanosphere (MS-CeO 2 ) as the support exhibited the most excellent performance. To reveal the reason behind this phenomenon, the calcination process of the catalyst precursor and the reaction process of toluene oxidation were investigated by in situ DRIFTS. It was found that the MnO 2 precursor and the type of catalyst support could have a large effect on the reaction pathway and the produced intermediates. Therefore, the roles of the MnO 2 precursor and the type of support should be key considerations when developing the high-performance MnO 2 -based toluene oxidation catalyst.