This study aimed at exploring the performance of the electro-Fenton (EF) process with a borondoped diamond (BDD) anode and an electrochemically exfoliated graphene-based cathode (EEGr), for removal of antibiotic ofloxacin (OFLO) from contaminated water. Compared with anodic oxidation (AO) process with BDD anode, the EF process with BDD anode (EF-BDD) could improve the decay kinetics of OFLO by 1.4-2.6 times and reduce the disposal cost by 28%-41%. Removal efficiency of TOC in EF-BDD process under 4.2 mA cm-2 was better than in AO process under 8.3 mA cm-2 , pointing out that the cost effectiveness of the EF process for mineralization of OFLO under low current density conditions. This advantage is due to the simultaneous formation of homogeneous (• OH) and heterogeneous (BDD(• OH)) hydroxyl radicals in the process. The synergistic factor of • OH and BDD(• OH) for mineralization of OFLO decreased with the current density rising from 4.2 (0.28) to 16.6 mA cm-2 (-0.08). Decay kinetics of OFLO in the EF-BDD and AO were more converging under higher current densities owing to the production of large amount of BDD(• OH). In the EF-BDD, a trade-off should be considered between accumulated BDD(• OH) on the surface of BDD anode and H2O2 generation on the cathode. Absolute rate constant for oxidation of OFLO by • OH (kOFLO) was calculated to be 3.86 × 10 9 M-1 s-1. Evolution of carboxylic acids and inorganic ions as well as toxicity assessment were followed during the treatment of OFLO solutions. Results obtained proved that the EF-BDD process is outstanding for oxidative degradation of OFLO thanks to the synergistic effect of •OH and BDD(• OH). These very strong oxidants being non-selective, this result can be extended to the treatment of antibiotic organic pollutants.