In this study, the anti-depressant Venlafaxine, a new emerging contaminant of interest for the Swiss legislation, was subjected to systematic degradation. In order to develop an efficient framework for the treatment of emerging contaminants at industrial scale by AOPs, the photo-Fenton process was employed and the effect of the concentration of the Fenton's reagents and the implication of the operating pH was assessed. Initially, in order to acquire a simple model that describes the process, a ( general) full factorial experimental design was implemented. Generally, Venlafaxine degradation was achieved in minutes range at pH = 3 and increased with higher pH values. However, the changes in pH inflicted considerable modification in the treatment efficiency and imposed the subsequent use of higher order models, obtained by response surface methodology ( 3 pH-specific central composite designs). The improved, respective second degree models created for the 3 categories of response variables ( kinetics, efficiency, Fenton evolution) were used as input for the desirability functions, towards the statistical optimization of the process. The composite desirability values obtained indicated the optimal operating regions ( 9 mg/L iron and 28 mg/L H2O2), thus contributing to efficient application of the photo-Fenton process. The developed approach can be used as framework when the optimal treatment conditions of new, emerging contaminants are sought at production level, through well-established advanced oxidation processes and effective statistical methods. (C) 2016 Elsevier Ltd. All rights reserved.