This study presents a combined photochemical (Fenton) and biological flow reactor for the degradation of p-nitrotoluene-ortho-sulfonic acid (p-NTS). This compound is contained in wastewaters coming from manufactures of dyes, surfactants and brighteners. The non-biodegradability of p-NTS in a fixed bed reactor (FBR) was proved under theoretically favourable conditions such as the presence of cosubstrates and adapted bacteria. From this ascertainment, p-NTS can be considered as a non-biodegradable compound. Afterwards, several experiments for sole photo-Fenton treatment were carried out in a laboratory scale photoreactor. By way of Dissolved Organic Carbon (DOC) and HPLC techniques, it was found that mineralization of p-NTS via photo-Fenton treatment in continuous or batch mode is not a cost-effective strategy. However, the chemical and biological characteristics studied for the phototreated samples showed that the Fenton system produced within a short time intermediates with very oxidised functional groups that are biodegradable and non-toxic. This thus could permit the integration of photochemical and biological processes. During treatments in continuous mode it was found that the main inconvenience of this application is related to the difficulty to control the H2O2 concentration. With this system, it was hard to avoid the inhibition of bacteria and hence a low biodegradation efficiency. To overcome the inconveniences of the process mentioned above, the semi-continuous mode was applied. The coupled photochemical-biological reactor was operated at five different treatment times (respectively 50, 70, 95, 110 and 125 min). It was found that the most interesting zone for the coupled treatment is at the beginning of the photo-pretreatment when time is short enough to achieve a cost efficient process and high biological and overall efficiencies. However, if the pre-treatment time is too short (i.e., 50 min), the intermediates present in the solution are still structurally close to the initial biorecalcitrant compound and the efficiencies of both, the biological-and whole coupled process are dramatically diminished. Consequently, the optimal time to stop the photochemical treatment before leading the treated water to the biological reactor was found to be 70 min. At this moment, appropriate efficiencies were reached giving the best compromise between time and energy (71 $US per cubic meter) invested in both the biological and the overall treatment.