Because of many variables and strong coupling effects between the reaction and distillation processes, the parameters optimization of reactive distillation (RD) process is usually a challenge work. In this study, response surface methodology (RSM) was used to design the numerical experiments and analyze process parameters of the methyl tertiary butyl ether (MTBE) reactive distillation column. Firstly, Packett-Burman design was employed to screen the significant process parameters affecting the conversion of isobutene from 10 variables. Then, a Steepest Ascent method and Box-Behnken design were applied to determine the optimum key process parameters, with maximizing the conversion of isobutene as an objective. The optimum and actual conversion of isobutene were 100 % and 97.54 % which is higher than a conversion of 91.95 % in the literature, under optimum conditions in MTBE reactive distillation process.