The porous structured zinc oxide (ZnO) microspheres decorated with silver nanoparticles (Ag NPs) have been fabricated as surface-enhanced Raman scattering (SERS) substrate for ultra-sensitive, highly reproducible and stable biological/chemical sensing of various organic molecules. The ZnO microspheres were hydrothermally synthesized without any template, and the Ag NPs decorated on microspheres via photochemical reaction in situ, which provided stable Ag/ZnO contact to achieve a sensitive SERS response. It demonstrates a higher enhancement factor (EF) of 2.44 x 10(11) and a lower detection limit of 10(-11) M-10(-12) M. This porous SERS substrate could also be self-cleaned through a photocatalytic process and then further recycled for the detection of same or different molecules, such as phenol red (PhR), dopamine (DA) and glucose (GLU) with ultra-low concentration and it possessed a sensitive response. The excellent performances are attributed to morphology of porous microspheres, hybrid structure of semiconductor/metal and corresponding localized field enhancement of surface plasmons. Therefore, it is expected to design the recyclable ultra-sensitive SERS sensors for the detection of biological molecules and organic pollutant monitoring. (C) 2017 Published by Elsevier B.V.