In this study, a Taguchi design of experiments was employed to systematically investigate the effect of five selected process input variables (i.e., illumination flux, aeration rate, CO2 supply rate, NaNO3-nitrogen source-concentration and salinity) on the cultivation profile of Stichococcus sp. The process response variables were the concentrations of biomass, carbohydrates, proteins, lipids and total products. Through a sensitivity analysis study, aeration was found to have the major effect on biomass growth and carbohydrates accumulation. On the other hand, the production of proteins and total products was significantly affected by NaNO3, while the lipids accumulation was triggered primarily by CO2. From the statistical analysis of the experimental data, a regression model was developed, correlating the concentrations of biomass and biochemicals with the process input variables. Three individual operating policies, maximizing the concentrations of either biomass-carbohydrates, or proteins-total products, or lipids, were simulated and experimentally verified. The second operating policy complies more with the operation of a potential biorefinery plant. Under this strategy, the cultivation of Stichococcus sp. resulted in biomass and total products concentrations equal to 3.20 and 2.51 g L-1, respectively. The mass fractions of these biochemicals with respect to the dry biomass were: carbohydrates 40.63%, proteins 26.25% and lipids 11.56%. (C) 2016 Elsevier Ltd. All rights reserved.