Although single atom catalysts (SACs) have been recognized as a prospective catalyst in advanced oxidation processes (AOPs) via persulfate activation, they still confronted with the issues of metal atoms aggregation and limit loading amounts. For addressing these issues, single Co atoms that incorporated on Fe-Ni layered double hydroxides (FeNi-LDHs) with oxygen vacancies is fabricated. Employing it as the support of Co atoms can not only minimize the aggregation of single metal atoms but also conductive to increase their loading amounts (up to 3.26 wt%), which is expected to display an unprecedented catalytic activity. 100% of TC (20 mg/L) can be eliminated within 5 min in Co-FeNi-LDH/PMS system. Radical and nonradical pathway collectively contributed to the TC elimination in Co-FeNi-LDH/PMS system, in which the electron transfer process in nonradical pathway is confirmed as the dominate mechanism via electrochemical studies and quenching experiments. PMS was adsorbed by Co-FeNi-LDH to form a Co-FeNi-LDH/PMS* complex during the PMS activation. Subsequently, TC is decomposed by transferring electrons to the Co-FeNi-LDH/PMS* complex via “donor-acceptor complex” mechanism. Benefiting from this mechanism, the Co-FeNi-LDH/PMS system displays superior anti-interference capability against inorganic anions. This study provides a unique insight on the skillful design and application of SACs.