Organophosphates (OPs) are highly toxic compounds used as pesticides and nerve agents. The devastating effects, reported in different studies, on the environment and human health indicate a serious scenario for both instantaneous and long terms effects. Bio-based strategies for OPs degradation seem the most promising solutions, particularly when extremophiles enzymes are used. These systems permit OPs degradation with high efficiency and specificity under mild conditions. However, as frequently observed, enzymes can easily lose activity in batch systems, so that a strategy to improve biocatalyst stability is highly needed, in order to develop continuous systems. In this work, for the first time, a continuous biocatalytic system for organophosphates (OPs) detoxification has been proposed by using a triple mutant of the thermostable phosphotriesterase (named SsoPox) isolated from the hyperthermophilic archaeon Sulfolobus solfataricus. The enzyme was covalently immobilized on polymeric membranes to develop a biocatalytic membrane reactor (BMR) able to hydrolyse a pesticide (paraoxon) contained in water. High paraoxon degradation (about 90%) and long term stability (1 year) were obtained when the enzyme was covalently immobilized on hydrophilic membranes. On the contrary, the enzyme in batch system completely loses its activity within few months after its solubilisation in buffer.