Lignocellulosic biomass can serve as raw material for ethanol production. However, lignocellulosic biomass is a complex mixture of carbohydrates that need additional processes for efficient ethanol production, such as pretreatment and hydrolysis before fermented into ethanol. Therefore, this work mainly focused on the creation and simulation of a model of ethanol production from Jerusalem artichoke stalk (JAS) following experimental data and using the commercial software ASPEN Plus with and without a heat exchanger network (HEN). Alkaline hydrogen peroxide pretreatment (AHP) was the first step for this process. The optimal conditions of AHP were a mixture of 2% w/w sodium hydroxide (NaOH) and 4% v/v hydrogen peroxide (H2O2) at 10% (w/v) solid-liquid ratio and 121°C for 90 min. After treatment, 10% AHP-JAS loading was fed to enzymatic hydrolysis at 50°C and the fermentation process at 30°C. The simulation suggested that a feedstock of 60,000 kg of JAS could yield 3,482.16 kg ethanol. The purification section by the extractive distillation system had 12 stages, a distillate to feed mole ratio (D/F) of 0.13, and a reflux mole ratio (R/R) of 1.5. The purity of the ethanol product was higher than 97 wt%. After the model simulation, HEN was designed by using Aspen Energy Analyzer. After the installation of HEN in this process, the ethanol plant with HEN showed a better result, which at 16.24 percentages reduced total cost compared to the process without HEN.