In this work, the laccase from Trametes versicolor was immobilized in highly porous silica monoliths (0.6 cm diameter, 0.5 cm length). These monoliths feature a unique homogeneous network of interconnected macropores (20 μm) with mesopores (20 nm) in the skeleton and a high specific surface area (330 m 2 /g). The enzymatic monoliths were applied to degrade tetracycline (TC) in model aqueous solutions (20 ppm). For this purpose, a tubular Flow-Through-Reactor (FTR) configuration with recycling was built. The TC degradation was improved with oxygen saturation, presence of degradation products and recirculation rate. The TC depletion reachs 50% in the FTR and 90% in a stirred tank reactor (CSTR) using crushed monoliths. These results indicate the importance of maintaining a high co-substrate concentration near active sites. A model coupling mass transfers with a Michaelis-Menten kinetics was applied to simulate the TC degradation in real wastewaters at actual TC concentration (2.8 10-4 ppm). Simulation results show that industrial scale FTR reactor should be suitable to degrade 90% of TC in 5 h at a flow rate of 1 mL/min in a single passage flow configuration. Nevertheless, the process could certainly be further optimized in terms of laccase activity, oxygen supply near active sites and contact time.