The development of efficient defluorination technology is an important issue because the kind of emerging pollutant of hexafluoropropylene oxide dimer acid (GenX) as an alternative to perfluorooctanoic acid (PFOA) has the higher environmental risks. In the UV/bisulfite system, we first developed a hydrophobic confined α-Fe2O3 nanoparticle layer rich in oxygen vacancies, which accelerated the enrichment of HSO3- and GenX on the surface and pores through electrostatic attraction and hydrophobic interaction, retaining more hydrated electrons (eaq-) and rapidly destroying GenX under UV excitation. Especially, under anaerobic and aerobic conditions, the degradation percentage of GenX obtain nearly 100%, defluorination of GenX to 88 and 57% respectively. It was amazed to find that the three parallel H/F exchange pathways triggered by the rapid reactions of eaq- and GenX, which were unique to anaerobic conditions, improved the efficiency of fluoride removal and weaken the interference of dissolved oxygen and H+. Therefore, this study provided an available material and mechanism for sustainable fluoride removal from wastewater in aerobic and anaerobic conditions.