This paper deals with the advanced control of a side-stream distillation column removing benzene from a reformed gasoline stream. A multivariable control strategy based on two SISO schemes, each controlling the benzene concentration in an outlet stream has been developed. Each SISO loop is a cascade one and consists of a secondary loop devoted to control pilot tray temperature and a primary inferential controller of the benzene composition based on a short-cut physical model. The decoupling between the two single loops was obtained by keeping the internal reflux between the side-stream tray and the bottom tray constant.