An experimental investigation is here presented on the photo-electrochemical removal of Methyl Orange (MO), selected as a model of the organic dyes, contained in wastewaters. The process is carried out in an electrochemical flow reactor, in which titania nanotubular electrode is irradiated with a simulated solar light. Design of Experiments (DOE) technique is used to plan the experimental campaign and investigate on the single and combined effects of applied current, electrolyte flow rate, and initial MO concentration, on the specific reaction rate. The results of the DOE analysis, also combined with the study of the distribution of the intermediate products, confirm a reaction mechanism mediated by OH radicals; high applied current and low reactant concentration resulted as favourable conditions to achieve high specific reaction rate of color removal.