Optimisation of reactive distillation (RD) process parameters is very important and complex because of a large number of variables and a strong coupling between them. A hybrid method of orthogonal numerical test and non-dominated sorting genetic algorithm II (NSGA-II) was presented for optimisation of the methyl tert-butyl ether (MTBE) RD process parameters such as the reflux ratio, the number of trays etc. on maximizing the conversion of isobutene and minimizing TAC of MTBE RD process simultaneously. Firstly, Aspen Plus was used to simulate MTBE RD process and the key parameters were selected by univariate sensitivity analysis. Secondly, the orthogonal test method was used to design the experiment scheme, and correlation formulations between the process parameters and objective functions (conversion of isobutene and total annual cost) were determined by second order regressions model according to the results of orthogonal numerical tests. Finally, based on the fitting function equations, NSGA-II was used to optimize the MTBE RD process parameters, and a non-dominated solution set was obtained and presented. The results indicate that the combination of orthogonal numerical test and the NSGA-II can not only reduce the number of experiments effectively, but also get the optimal and effective process parameters set for process design and operation.