Although microbial fuel cells (MFCs) have potential for high-salt wastewater treatment, their application is limited by poor salt tolerance, deactivation and unstable catalytic performance. This study designed Ce–C, N–C, and Ce–N modified activated carbon (Ce–N–C) based on the catalytic mechanism and salt tolerance performance of Ce and N elements to address these limitations. With activated carbon (AC) as the control, this study analyzed the stability of the four cathodes under different salinity environments using norfloxacin (NOR) as a probe to assess the effect of cathodes and salinity on MFC degradation performance. After three months, comparing with other three cathodes, the Ce–N–C cathode demonstrated superior and stable electrochemical and power generation performance. In particular, the advantages of Ce–N–C in high-salt (600 mM NaCl) environment is more significant than no-salt or low-salt. The potential of Ce–N–C-End at current density of 0 was 14.0% higher than AC-End, and the power density of the MFC with Ce–N–C cathode was 105.7 mW/m2, which was 3.1 times higher than AC. Also, the stability of NOR removal under the function of Ce–N–C improved with the increase of NaCl concentration or operation time. The CeO2(111) crystal form, N–Ce–O bond and pyridine N might be the key factors in improving the catalytic performance and salt tolerance of the Ce–N modified carbon-based cathode using XPS and XRD analysis.