An innovative conceptual design is introduced for lignocellulosic-based biochemical platform biorefi neries using three mixed-culture bioprocesses that sequentially disintegrate each polysaccharide fraction into different target biofuels: hydrogen, methane, and fuel butanol. This mixed-culture biorefi nery circumvents the use of corrosive chemicals, energy-demanding pre-treatments, costly enzymes, separate units for saccharifi cation and fermentation, steam for sterilization, and expensive steel bioreactors. The concept mimics bioprocesses occurring in nature to degrade complex substrates. A technoeconomic analysis of these biorefi neries is carried out focusing on the impact of residence times (8-120 h) and butanol titers (10-20 g/L) of the production of acetone-butanol-ethanol (ABE) on the total production costs (TPC) of butanol. The design includes electricity-steam cogeneration from gaseous biofuels and lignin, as well as solvent purifi cation. Simulation results show that the highest butanol titer impacts TPC to a greater extent than the lowest residence time. TPC range from US$1.04 to US$1.27 per liter of butanol in facilities with 20 g/L of butanol irrespective of residence time. The end-use energy ratio for all facilities was close to 2 or higher. These biorefi neries display lower energy consumption and environmental impacts than conventional second-generation lignocellulosic biofuels biorefi neries, and its cost structure is determined by the substrate similar to bioprocesses with mature technology. Finally, this study provides an insight to the advancements made in realizing viable mixed-culture fermentations for different fi elds of biotechnology and therefore might be encouraging for further studies of lignocellulosic biorefi neries based on mixed cultures.