This study was undertaken to investigate the degradation of 6-aminopenicillanic acid (6-APA) and cloxacillin in aqueous solution by the combined effect of subcritical water and the oxidising agents O-2, H2O2, and K2S2O8. Nano ZnO was used as a solid catalyst. Response surface methodology was used to determine the optimum experimental parameters (temperature, treatment time, and concentration of oxidising agent). For 6-APA, the maximum organic carbon (TOC) removal rates of 83.54%, 81.11% and 42.42% were obtained using H2O2, K2S2O8, and O-2, respectively. For cloxacillin, the maximum TOC removal rates of 67.69%, 76.02% and 14.45% were obtained using H2O2, K2S2O8, and O-2, respectively. Additionally, the impact of nano and commercial ZnO on TOC removal rates was determined. Secondary ions produced during the degradation processsuch as nitrite, nitrate, sulphate and chloridewere determined using ion chromatography.