Abstract: This work focuses on the purification section of a 24,000-ton-per-annum dimethyl sulfoxide (DMSO) production plant. A simulation model for the DMSO distillation column was developed using the non-random two-liquid (NRTL) property method, and process simulation and optimization studies were conducted. The initial relationship between the number of theoretical stages and the reflux ratio was determined using the shortcut method. Subsequently, a rigorous method, coupled with sensitivity analysis tools, was employed for the multi-objective optimization of key parameters, including the reflux ratio, feed stage location, and number of theoretical stages. An economic model was used to minimize the total annual cost (TAC) and balance capital investment with operational energy consumption. The results indicate that the optimal configuration consists of 25 theoretical stages, a feed location at the 17th stage, and a reflux ratio of 0.229, achieving a high DMSO product purity of 99.98% with the lowest total annual cost. Finally, hydraulic performance was verified, leading to the selection of Sulzer Mellapak 752Y/252Y structured packing and a column diameter of 0.7 meters. The flooding factor across the entire column remained within the safe operating range. This study provides a reliable theoretical basis and an optimized design strategy for achieving energy savings, reducing consumption, expanding capacity, and improving efficiency in industrial DMSO purification columns.