Laser-driven relativistic electrons can be focused onto a high-Z convertor for generating high-brightness γ-rays, which in turn can be used to induce photonuclear reactions. In this work, photo-transmutation of long-lived radionuclide 135Cs induced by laser–plasma–interaction-driven electron source is demonstrated using Geant4 simulation (Agostinelli et al., 2003 Nucl. Instrum. Meth. A506, 250). High-energy electron generation, bremsstrahlung, as well as photonuclear reaction are observed at four different laser intensities: 1020, 5 × 1020, 1021, and 5 × 1021 W/cm2. The transmutation efficiency depends on the laser intensity and target size. An optimum laser intensity, namely 1021 W/cm2, was found, with the corresponding photonuclear reaction yield reaching 108 J−1 of the laser energy. Laser-generated electrons can therefore be a promising tool for transmutation reactions. Potential application in nuclear waste management is suggested.