In this work an industrial Biomass-To-Liquid(BTL) plant simulation and optimization are presented. Biomass is first gasified with oxygen and steam, and the produced syngas is fed to a multi-tubular fixed bed reactor for Fischer-Tropsch (FT) synthesis, obtaining a distribution of hydrocarbons with different molecular weight. A simplified model for the biomass gasification section is implemented in HYSYS V8.4, while the Fischer-Tropsch reactor is simulated using MATLAB (R) R2013a. The kinetic parameters of the FT reaction have been determined by using a non-liner regression performed with the experimenta data obtained with a bench-scale FT-rig. The model developed for the Fischer-Tropsch reactor takes into account the catalytic pellet's effectiveness factor and the eventual formation of a liquid phase in each point along reactor's axial coordinate. The whole BTL plant is simulated connecting MATLAB and HYSYS. Moreover, the staging of the Fischer-Tropsch reactor is studied performing a techno-economic analysis of three different plant configurations and evaluating the corresponding pay-back time. (C) 2017 Elsevier Ltd. All rights reserved.