The performance of oxidative desulfurization (ODS) of commercial diesel by alumina supported polymolybdate based catalyst system was studied using tert-butyl hydroperoxide (TBHP) as an oxidizing agent. From catalytic testing, MoO3-Al2O3 calcined at 500 oC was the most potential catalyst which gave the highest sulfur removal under mild condition. The sulfur content in commercial diesel was successfully reduced from 440 ppmw to 105 ppmw followed by solvent extraction. Response surface methodology involving Box-Behnken was employed to evaluate and optimize MoO3/Al2O3 preparation parameters (calcination temperatures, molybdenum loading precursor and catalyst loading), and their optimum values were found to be 510 oC, 0.98 g and 11.18 g/L of calcination temperature, molybdenum loading precursor and catalyst loading, respectively. Based on results, the reaction mechanism for oxidation of sulfur compounds to the corresponding sulfones occur in the presence of MoO3 /Al2O3 catalyst was proposed.