A kind of high-performance self-powered broad-band photodetectors throughout UV/visible/near-infrared wavelengths have been fabricated based on CdS:P3HT microwires. The fabricated devices exhibit fast responses and excellent sensitivities to UV/visible/near infrared light illumination at zero bias. Together with the fast response and high sensitivity, the photocurrent under UV illumination can be increased to more than 330% when applying a 0.67% tensile strain under the [001] direction point of CdS microwire contacting with P3HT. This enhancement through the piezo-phototronic effect can be attributed to the increase of built-in field at the interface of p-n junction, which is favorable to the separation of photogenerated electron-hole pairs in CdS and P3HT. In comparison, the photocurrent under UV illumination can be decreased to ~ 20% when applying a 0.67% tensile strain under the [001¯] direction point of CdS microwire which contacts with P3HT. This research not only focuses on the photoelectric property of organic-inorganic hybrid semiconductors, but also combines it with piezoelectric effect to modulate the performance of optoelectronic devices made of piezoelectrical semiconducting materials.