Piezo-phototronic devices, where optoelectrical properties are directly influenced by mechanical stimuli, are highly desirable for applications in wearable devices and human-machine interfaces. Here, the piezoelectric and piezo-phototronic properties of GaSe nanosheets, a layered metal-monochalcogenide III-VI semiconductor with interesting piezoelectric, optical excitation, and semiconducting properties are investigated. A giant piezo-phototronic response in GaSe is demonstrated for the first time. The out-of-plane local field due to band gap modulation drives the electrons (holes) to move toward the outer (inner) surface of wrinkles, which enhances electron-hole pair generation and the related photocurrent. Moreover, manual bending of GaSe reliably enhances the photocurrent by more than a factor of 50 at room temperature. This giant and linear piezo-phototronic response combined with excellent stretchability suggests that GaSe is a valuable material for flexible optoelectronic-mechanical applications.