During the outbreak of water blooms, extracellular organic matters (EOM) of algae accumulates in water bodies, causing great risks to water treatment processes and effluent quality. EOM is different to remove using conventional water treatment technologies, and secondary disinfection by-products may significantly affect the quality of the water supply. Therefore, it is urgent to develop efficient water treatment technologies to degrade EOM. Vacuum ultraviolet (VUV) can generate reactive oxidative species (ROS) in situ to remove organic pollutants, so it has the potential to remove EOM. In this study, vacuum ultraviolet (VUV)-activated persulfate (PS) was used to remove EOM, and its treatment efficiency, influencing factors, reaction mechanism, and impact on the formation of disinfection by-products (DBPs) were investigated, aiming to apply it to the treatment of natural algae-containing water. The results revealed that the VUV/PS system can rapidly degrade and mineralize EOM, with a removal rate of 93.7% for UV₂₅₄ and 74.1% for DOC respectively. The degradation rate of EOM significantly increases as the dosage of PS increases, and acidic conditions promote the degradation and mineralization efficiency of EOM. The coexisting HCO-₃ and Cl- in water significantly inhibit the mineralization efficiency of the VUV/PS system for EOM, while the influence of NO-₃ is relatively small. As VUV irradiation promotes the generation of ROS, the concentrations of hydroxyl radicals (HO^·) and sulfate radicals (SO^·-₄) in the VUV/PS system are higher than those in the UV/PS system. The efficient mineralization of EOM in the VUV/PS system is mainly attributed to HO^· and sulfate radical SO^·-₄. Dissolved oxygen effectively promote the degradation of EOM by facilitating the generation of ROS, primarily HO^· and SO^·-₄. After treatment with VUV/PS, the generation amount of DBPs in the subsequent chlorination disinfection process decrease significantly. The VUV/PS system demonstrates the ability to significantly reduce the mass concentrations of UV_254, DOC in water and the generation amount of DBPs when treating natural algae-containing water.