In this study, the effect of phosphate, Fe(III), Fe(II), and reductive substances (i.e., Mn2+ and SO32-) on diclofenac (DCF) oxidation and its degradation mechanism by Ferrate (Fe(VI)) were investigated. The removal rate of DCF in reaction solution at pH 9.0 adjusted by NaOH (67.36%) was higher than that by phosphate buffer (14.87%) because of the complexation of phosphate with Fe(III) and/or Fe(II) restraining the self-catalysis of Fe (VI). Fe(III) or Fe(II) could significantly catalyze Fe(VI) to generate more intermediates (i.e., Fe(V) and Fe(IV)), whose oxidation capacity was magnitude stronger than that of Fe(VI), leading to the improvement of DCF degradation, besides, the presence of reductive substances, e.g., Mn2+ and SO32-, could also increase the self catalysis of Fe(VI), enhancing the removal of DCF, which will be further verified in follow-up studies. Seven oxidation products (OPs) were detected using a quadrupole-time of flight-mass spectrometer coupled with an ultra performance liquid chromatograph (LC-QTOF/MS). Based on these identified OPs, the potential degradation mechanism of DCF by Fe(VI) was proposed showing six reaction pathways, including hydroxylation, decarboxylation, C-N bond cleavage, dehydrogenation, formylation, and dechlorination-hydroxylation. This study suggests that Fe(VI) can effectively oxidize and degrade DCF.