The degradation of oxacillin in aqueous solution by strong ionization dielectric barrier discharge (DBD) was explored. The effects of input voltage, initial pH, initial concentration of solution and hydroxyl (·OH) inhibitor on the removal efficiency of OXA were investigated. The results showed that the removal efficiency of OXA with initial concentration of 20mg/L reached 91.5% under the optimal treatment conditions of 3.8 kV and 7.3 pH. With the higher voltage and the lower initial concentration, the removal effect was better. The pH of the solution has little effect on the removal efficiency, and the removal effect is the best in neutral aqueous solution. The inhibition effect of TBA was stronger than that of CO32- and HCO3-. Moreover, ·OH was the main active substance in the process of strong ionization discharge, which played a major role in the removal of OXA. In addition, two main by-products were identified, the transformation pathways including hydroxylation (+16 Da), decarboxylation (-44 Da) were observed. This study provided a theoretical basis for the effective removal of antibiotics in water by strong ionization discharge.