The phosphorus tungsten(PW) heteropoly acids were immobilized on the mesoporous molecular sieves(MCM-41) by wet impregnation. The prepared catalysts were characterized by X-ray powder diffraction, TG and DTA,FTIR. The alkylation of p-cresol with isobutylene was carried out over the PW /MCM-41 catalysts. The influences of various reaction parameters such as reaction temperature, time, PW loading, and catalysts amount on the conversion of p-cresol and the products selectivity were also investigated. Under the optimized reaction conditions of 90 °C,PW loading of 10%, catalyst amount of 1.5%, p-cresol conversion was found to be 93.89% with product rate to 2-tert-butyl-p-cresol 51.29%, 2,6-di-tert-butyl-p-cresol 42.48% and tert-butyl-p-tolyl ether 0.12%, responding to selectivity of 2, 6-di-tert-butyl-p-cresol 45.24%.