The ability of decatungstate anion (W10O324-) to photoproduce OH center dot radicals from water is retained when the polyoxoanion is immobilized on solid supports and can be exploited as a heterogeneous photocatalytic process aimed to water remediation. However, we show that interaction between OH center dot radicals and drug molecules depends on the physical chemical properties of the chosen support. In fact, we demonstrate that silica particles covered by decatungstate anions are not efficient in the degradation of carbamazepine and sulfamethoxazole (ubiquitary contaminants of natural waters) that are respectively neutral and negatively charged at operating pH of 6. On the contrary, entrapment of W10O324- inside a mesoporous organosilica matrix leads to a heterogeneous photocatalytic system with proper characteristic of hydrophobicity. Organic molecules enter mesopores and easily leave the aqueous environment. Inside pores, the reaction between photoproduced OH center dot radicals is favored. Mono- and di-hydroxylated products precede fragmentation and degradation of the investigated drug.