For the first time，a novel method to synthesize acetone from isobutane and oxygen is proposed. Tert-butyl hydroperoxide (TBHP) is generated from isobutane and oxygen firstly, and then TBHP is catalytically decomposed to acetone. The optimal reaction conditions, catalytic system, stability and recyclability of the catalyst, and the causes of catalyst deactivation for the catalytic decomposition of TBHP to acetone were investigated. The results indicated that the acid property of the zeolite catalysts had a very obvious influence on reaction activity. The β zeolite possesses the optimal catalytic activity (100 % conversion) and the selectivity to acetone (49 wt%) than Y zeolite and ZSM-5 zeolite. Furthermore, the selectivity to acetone decreased significantly during the 30 h-reaction cycle with the catalyst of β zeolite, indicating that the catalyst was less stable. Moreover, the catalytic performance of β zeolite can be fully recovered even after regenerating for 5 times. By pretreating the catalyst with different products, it was determined that further reaction of acetone was the main reason for catalyst deactivation; the stability of the reaction for 30 h was significantly improved by diluting the feedstock with ethanol, and the catalyst"s reactivity as well as reusability were not affected.