Fe loading 3D micro-meso-porous carbon sphere (Fe@3C-2N) was derived from natural cellulose of sawdust and melamine through sodium alginate and ferric chloride cross-linking followed by carbonization processes, which served as peroxymonosulfate (PMS) activators for enrofloxacin (ENR) degradation. The cellulose was produced by the delignification of sawdust with sodium chlorite. The delignification of sawdust and the addition of melamine increased the porosity and electron transport capacity of Fe@3C-2N. When the dosages of Fe@3C-2N and PMS were 0.60 g L−1 and 0.20 g L−1 respectively, the degradation rate of ENR (20 mg L−1) reached 92.17 % within 80 min, suggesting the satisfactory activation performance of PMS. The good structural stability of Fe@3C-2N makes it suitable for use as packing in continuous flow reactors for wastewater treatment. Quenching experiments and electron paramagnetic resonance (EPR) suggested that SO4•− and 1O2 were the dominant reactive oxygen species (ROSs) in Fe@3C-2N/PMS system. X-ray photoelectron spectroscopy (XPS) revealed that Fe3C, pyrrolic N and graphitic N were the potential active sites.