The Response Surface Methodology (RSM) was applied as a tool for the optimization of the operational conditions of the photo-degradation of highly concentrated PY12 wastewater, resulting from a textile industry located in the suburbs of Medellin (Colombia). The Box-Behnken experimental Design (BBD) was chosen for the purpose of response optimization. The photo-Fenton process was carried out in a laboratory-scale batch photo-reactor. A multifactorial experimental design was proposed, including the following variables: the initial dyestuff concentration, the H(2)O(2) and the Fe(+2) concentrations, as well as the UV wavelength radiation. The photo-Fenton process performed at the optimized conditions resulted in ca. 100% of dyestuff decolorization, 92% of COD and 82% of TOC degradation. A kinetic study was accomplished, including the identification of some intermediate compounds generated during the oxidation process. The water biodegradability reached a final DBO(5)/DQO = 0.86 value.