In this study, the anaerobic treatment and microbial characteristics of high-concentration cephalosporin wastewater were studied. A pilot-scale expanded granular sludge bed (EGSB) reactor was designed to treat cephalosporin wastewater, whose diameter, height and effective volume were 0.5 m, 4.9 m, 0.92m(3), respectively. With mixed high-concentration cephalosporin wastewater and municipal wastewater as a substrate, the anaerobic reactor was started and operated 414 days. An average COD removal efficiency of 72% was achieved at an organic loading rate (OLR) of 9.96 kg COD/(m(3).d), with a hydraulic retention time (HRT) of 25 h. The average methane content reached 82%. Methanobacterium and Methanomassiliicoccus were predominant archaea in the granular sludge for each of the organic loading rates, and the predominant methane-producing pathway was hydrogenotroph and methylotroph. Those results demonstrated that the EGSB reactor could treat high-concentration cephalosporin wastewater with a unique methane-producing pathway.