The reuse of powdered activated carbon (PAC) vitally determines the economics and security of the PAC-based adsorption process, while state-of-the-art PAC regeneration technologies are usually unsatisfactory. Here, it is demonstrated that isolated Fe sites anchored on commercial PAC enable fast H 2 O 2 activation to produce Fe-based reactive oxygen species for highly efficient PAC regeneration at room temperature. Taking rhodamine B as a representative pollutant, PAC decorated with isolated Fe sites realize H 2 O 2 based regeneration with negligible adsorption capacity degradation for 10 cycles. Moreover, in terms of the PAC loss rate, this technology is greatly superior to traditional Fenton-based regeneration technology. Further operando experiments and theoretical calculations reveal that the high regeneration performance can be attributed to the isolated HOFeO motifs, which activate H 2 O 2 via a nonradical reaction pathway. These findings provide a very promising strategy toward reducing the cost of H 2 O 2 -based PAC regeneration technology.