The presence of selenium vacancies (V Se ) in metal selenides enables the activation of peroxymonosulfate (PMS) for efficient water purification. However, the mechanisms of interactions of V Se with PMS and organic pollutant removal are unclear. Hence, we precisely prepared a series of FeSe 2 @MoO 3 composites with V Se for effective activation of PMS for the removal of various organic pollutants. The roles of V Se are explored via density functional theory (DFT) calculations: (i) regulating the electron distribution of Fe and Mo orbitals in FeSe 2 @MoO 3 for enhancing the PMS adsorption and (ii) promoting the conversion of transition metallic redox pairs (Fe 3+ /Fe 2+ and Mo 6+ /Mo 5+ / Mo 4+ ). The as-prepared FeSe 2 @MoO 3 -8 exhibits excellent catalytic performance via PMS activation in which nearly 100% removal efficiencies of various organic pollutants are achieved within 2−10 min. The quenching experiments, electronic spin resonance (ESR), and probe tests demonstrated that the multiple reactive species like SO 4•− , O 2 •− , • OH, and 1 O 2 contributed to the removal of 2,4-D. Finally, FeSe 2 @MoO 3 -8 was attached to the polyvinylidene difluoride (PVDF) membrane for continuous and efficient removal of 2,4-D, in which the removal efficiency and total organic carbon removal efficiency of 2,4-D were > 90% and >70% within 12 h of operation.