Surfactants are increasingly used in systems that come into contact with the human body, such as food, pharmaceuticals, cosmetics and personal hygiene products. Increasing attention is being devoted to the toxic effects of surfactants in various human contact formulations, as well as the removal of residual surfactants. In the presence of ozone (O3), anion surfactants—a characteristic micro-pollutant—such as sodium dodecylbenzene sulfonate (SDBS) in greywater, can be removed using radical advanced oxidation. Herein, we report a systematic study of the SDBS degradation effect of O3 activated by vacuum ultraviolet (VUV) irradiation and the influence of water composition on VUV/O3, and determined the contribution of radical species. We show a synergistic effect of VUV and O3, while VUV/O3 reached a higher mineralization (50.37%) than that of VUV (10.63%) and O3 (29.60%) alone. The main reactive radicals of VUV/O3 were HO•. VUV/O3 had an optimal pH of 9. The addition of SO42− had almost no effect on the degradation of SDBS by VUV/O3, Cl− and HCO3− slightly reduced the reaction rate, and NO3− had a significant inhibition on the degradation. In total, SDBS had three isomers, with which the three degradation pathways were very comparable. Compared with SDBS, the toxicity and harmfulness of the degradation by-products of the VUV/O3 process decreased. Additionally, VUV/O3 could degrade synthetic anion surfactants from laundry greywater effectively. Overall, the results show the potential of VUV/O3 in safeguarding humans from residual surfactant hazards.