The invention discloses a CrOx/mesoporous CaO catalyst for effectively preparing isobutene by oxidative dehydrogenation of iso-butane and a preparation method thereof, and belongs to the field of catalysis. The prior catalyst for preparing the isobutene by the oxidative dehydrogenation of the iso-butane has the problems of low isobutene selectivity and the like. The catalyst provided by the invention uses mesoporous CaO as a carrier and uses CrOx as an active component, wherein x is 1 to 3; and the loading capacity of the CrOx active component is 4 to 12 percent based on the mass percentage of Cr2O3.The preparation method comprises the following steps: dissolving soluble chromium salt into anhydrous ethanol, then adding the solution into the mesoporous CaO carrier, stirring the mixture evenly, and drying the mixture for 12 hours at 120 DEG C to obtain white solid powder; and heating the white solid powder to 550 DEG C at the rate of 1 DEG C per minute in air atmosphere in a muffle furnace, and firing the heated white solid powder for 3 hours at constant temperature to obtain the CrOx/mesoporous CaO catalyst. The CrOx/mesoporous CaO catalyst prepared by the method has high isobutene selectivity and high activity, and the preparation method has low cost and simple and convenient operation.