It's urgent to develop effective methods to remove antibiotics in environment, especially in drinking water. In this work, RGO/MoS2/Ce0.75Zr0.25O2 composite was prepared by hydrothermal self-assembly method and firstly used as cathode to degrade ciprofloxacin in electro-Fenton system. The removal of ciprofloxacin reached 100% within 5 h, and the mineralization rate achieved 77.1% in 3 h. The optimal degradation conditions were investigated, and the composite was fully characterized by SEM, XRD, BET, XPS, CV and EIS. The results showed that MoS2 and Ce0.75Zr0.25O2 nanoparticles were introduced onto RGO nanosheets successfully. Compared to RGO and RGO/MoS2 composites, the effective degradation performance of RGO/MoS2/Ce0.75Zr0.25O2 cathode was mainly associated with the enhanced electrochemical activities by doping MoS2, heterogeneous catalysis of Ce3+/Ce4+ on decomposition of H2O2, improved oxygen storage capacity owing to the formation of ceriazirconia solid solution, and effective electro-absorption of RGO. Analysis of H2O2 production and hydroxyl free radicals indicated the predominated role of 'OH in the electro-Fenton process. The degradation intermediates and the possible degradation mechanism were investigated in detail.