The distillation with side reactor has been proposed to remove sulfur compounds of diesel. The design and optimization of a hydrodesulfurization process involve the selection of the configuration and the operating conditions to minimize the total annual cost, CO2 emissions, and the amount of sulfur compounds. In general, the optimal design of a hydrodesulfurization process is a nonlinear and multivariable multiobjective optimization problem, with the presence of both continuous and discrete design variables. In particular, stochastic multiobjective optimization algorithms are capable of solving, robustly and efficiently, challenging optimization problems, and they appear to be a suitable alternative for the design and optimization of complex process schemes. In this study, we have performed the multiobjective optimization of five configurations of distillation with a side reactor for the hydrodesulfurization process including an alternative using reactive distillation. The multiobjective optimization problem can be stated as a minimization of total annual cost (TAC), CO2 emissions, and amount of sulfur compounds. The results obtained in the Pareto fronts indicated competition between total annual cost, CO2 emissions, and the amount of sulfur compounds of the hydrodesulfurization process. These Pareto solutions are useful to identify proper conditions for the operation of this process. In general, the reduction of the amount of sulfur compounds increases the TAC and CO2 emissions. However, we can identify operating conditions where the TAC can be reduced.