Cr 3+ and Zr 4+ cation-incorporated hydrotalcites (HTs) were prepared by coprecipitation method. Corresponding mixed oxide were obtained by the thermal decomposition of HTs at 773K for 8h and applied in the synthesis of isophorone (IP) from acetone. From the characteristic results, both Cr 3+ and Zr 4+ were introduced into the lattice of hydrotalcite producing the more disordered HT structures. Compared with Mg–Al mixed oxide, Cr and Zr modified mixed oxide demonstrated more amount of basic sites and stronger base strength, which were responsible for the improvement of catalytic activity. As a result, both of the modified mixed oxide exhibited IP selectivity of more than 70% under atmospheric pressure.