Bio-ethanol has received considerable attention as a basic chemical and fuel additive. Bio-ethanol is presently produced from sugar/starch materials, but can also be produced from lignocellulosic biomass via hydrolysis-fermentation route or thermo-chemical route. In terms of thermo-chemical route, a few pilot plants ranging from 0.3 to 67 MW have been built and operated for alcohols synthesis. However, commercial success has not been found. In order to realize cost-competitive commercial ethanol production from lignocellulosic biomass through thermo-chemical pathway, a techno-economic analysis needs to be done. In this paper, a thermo-chemical process is designed, simulated and optimized mainly with ASPEN Plus. The techno-economic assessment is made in terms of ethanol yield, synthesis selectivity, carbon and CO conversion efficiencies, and ethanol production cost. Calculated results show that major contributions to the production cost are from biomass feedstock and syngas cleaning. A biomass-to-ethanol plant should be built around 200 MW. Cost-competitive ethanol production can be realized with efficient equipments, optimized operation, cost-effective syngas cleaning technology, inexpensive raw material with low pretreatment cost, high performance catalysts, off-gas and methanol recycling, optimal systematic configuration and heat integration, and high value byproduct. (C) 2010 Elsevier Ltd. All rights reserved.