Optofluidic nano/microsystems have advanced the realization of Boolean circuits, with drastic progression to achieve extensive scale integration of desirable optoelectronics to investigate multiple logic switches. In this context, we demonstrate the optofluidic logic operations with interfacial piezophototronic effect to promote multiple operations of electronic analogues. We report an optofluidic Y-channeled logic device with tunable metal-semiconductor-metal interfaces through mechanically induced strain elements. We investigate the configuration of an OR gate in a semiconductor-piezoelectric zinc oxide nanorod-manipulated optofluidic sensor, and its direct reconfiguration to logic AND through compressive strain-induced (−1%) piezoelectric negative polarizations. The exhibited strategy in optofluidic systems implemented with piezophototronic concept enables direct-on chip working of OR and AND logic with switchable photocurrent under identical analyte. Featured smart intrinsic switching between the Boolean optoelectronic gates (OR↔AND) ultimately reduces the need for cascaded logic circuits to operate multiple logic switches on-a-chip. © 2019, The Author(s).