Recently, developing a catalyst system without the demand of light irradiation has received a great attention. Here, we report the new advances in the piezoelectric properties of two-dimensional MoSe₂ in the application of degradation and further investigate the reactive oxygen species as results from the active sites of the single- and few-layered structure. This work successfully synthesized non-centrosymmetric single- and few-layered MoSe₂ nanoflowers by a hydrothermal method. The single- and few-layered structure of MoSe₂ nanoflowers were discovered to have a highly efficient piezo-catalyst effect, which possessed a superior piezo-catalyst activity toward decomposition of Rhodamine B dye by imposing an ultrasonic-wave in the dark. In the presence of mechanical force, the spontaneous polarization establish an internal electric field in the non-centrosymmetric structure, which acts as an efficient driven force for the separation of the electrons and holes in an opposite direction. Consequently, the surface of polarized MoSe₂ nanoflowers emerges the strain-induced charges that are available for generating hydroxyl radical to oxidize the Rhodamine B dye. The piezoresponse force microscopy (PFM) and the tunneling atomic force microscopy (TUNA) confirmed that the MoSe₂ nanoflowers exhibited a significantly piezoelectric potential. The electron paramagnetic resonance (EPR) spectra further proved that the hydroxyl radicals were generated when the mechanical force applied to the nanoflowers. The degradation ratio reached 100% within 120 s for destroying the Rhodamine B dye and showed an ultra-fast degradation rate at 69,889 ppm L mole ⁻¹ s ⁻¹. Compared to the commercial bulk MoSe₂, the nanoflowers showed a better performance due to the single layer and odd layer structure as observed in the HRTEM images. Furthermore, the piezocatalytic effect of MoSe₂ nanoflowers has a potential in exhibiting an efficient piezocatalytic activity in hydrogen evolution. Ultrasonic waves lead to a strain-induced electrons and holes on their surface, which create the redox reaction on the water molecules. The higher amount of hydrogen gas output has been observed at the higher frequency of ultrasonic-wave system. This work provides a great possibility for the future application in hydrogen production by using energy waste from the environment, such as vibration. In summary, this research demonstrates the evident structure of single- and few-layered MoSe₂ nanoflowers with piezoelectric potential output and reveals the fastest degradation rate among the reported value. In addition, the piezo-catalyst effect of MoSe₂ nanoflowers offers a future promising candidate for hydrogen production.