The inhibitors produced in the pretreatment (phenolics, furans, and organic acids) as well as in the fermentation (butanol and organic acids) limit acetone, butanol, and ethanol (ABE) production from lignocellulose. To reduce their negative impact on the fermentation, a process involving simultaneous saccharification, ABE fermentation, and detoxification by liquid-liquid extraction was proposed and economically optimized. Although several extractants may be used to reduce butanol toxicity increasing the reactor performance, simultaneous detoxification of inhibitors from pretreatment (IFP) is difficult due to their high boiling point. Hence, the simultaneous detoxification system was evaluated using the biocompatible extractant: oleyl alcohol (boiling point of similar to 350 degrees C). Given that oleyl alcohol and IFP have a high boiling point, a heat-integrated distillation system with low-pressure columns was proposed to reduce the energy requirements of the purification of IFP and products from the fermentation. The simulations were performed rigorously in Aspen Plus' and Matlab. at different concentrations of IFP. Although IFP and butyric acid production become feasible ABE production by SSF-E at concentrations of IFP between 13.5 and 30 g/l, the energy requirements were between 1.2- and 2.4-fold higher than that for IFP concentrations of 9 g/l, respectively.