A series of MoBiFeCoK mixed-oxide catalysts were prepared by the co-precipitation method using (NH4)6Mo7O24·4H2O, Bi(NO3)3·5H2O, Fe(NO3)3·9H2O, Co(NO3)2·6H2O , and KNO3 as the precursor metal salts to investigate the relative contents of the main metals Mo and Bi, the co-metals Fe and Co, and the doped K. The performance of the catalysts for the gas-phase oxidation reaction of isobutene was investigated. The relative contents of the main metals Mo and Bi, the co-metals Fe and Co, and the doped metal K were investigated to determine the performance of the catalysts in catalyzing the gas-phase oxidation reaction of isobutene. The catalysts before and after doping with K were characterized by SEM, EDX, XRD, and NH3-TPD, and the catalysts were optimized to catalyze the reaction conditions of the gas-phase oxidation reaction of isobutene and tested for the catalytic stability of the catalysts for 100 h. The results showed that the relative contents of Bi, Fe, Co, and K had a significant effect on the catalytic performance of MoBiFeCoK mixed-oxide catalysts for the gas-phase oxidation reaction of isobutene, with Mo12Bi1.2Fe3Co8K0.4 showing the optimal catalytic performance; the NH3-TPD characterization showed that the doping of K lowered the amount of the acid center of the catalysts (from 15.27 μmol/g of Mo12Bi1.2Fe3Co8 to 5.91 μmol/g of Mo12Bi1.2Fe3Co8K0.4) and significantly enhanced the selectivity of the main product methacrolein (MAL); the optimal conditions for the gas-phase oxidation reaction of isobutene were as follows: 0.66 g of Mo12Bi1.2Fe3Co8K0.4 as catalyst, reaction temperature of 320 ℃, n(O2):n(isobutene) (oxygen-alkene ratio)=10:1, and volume-air velocity (GHSV)=2000 h-1. The catalytic isobutene gas-phase oxidation reaction of Mo12Bi1.2Fe3Co8K0.4 was stable for 100 h, and the isobutene conversion was maintained at 98.6%, and the selectivity of MAL was maintained at 86.4%.