It is known that many kinds of fermentative antibiotics can be removed by temperatureenhanced hydrolysis from production wastewater based on their easy-to-hydrolyze characteristics.However,a few aminoglycosides are hard to hydrolyze below 100℃ because of their stability expressed by high molecular energy gap (△E).Herein,removal of hard-to-hydrolyze kanamycin residue from production wastewater by hydrothermal treatment at subcritical temperatures was investigated.The results showed the reaction temperature had a significant impact on kanamycin degradation.The degradation half-life (t1/2) was shortened by 87.17-fold when the hydrothermal treatment temperature was increased from 100℃ to 180℃.The t1/2 of kanamycin in the N2 process was extended by 1.08-134-fold compared to that of the corresponding air process at reaction temperatures of 140-180℃,indicating that the reactions during hydrothermal treatment process mainly include oxidation and hydrolysis.However,the contribution of hydrolysis was calculated as 75％-98％,which showed hydrolysis played a major role during the process,providing possibilities for the removal of kanamycin from production wastewaters with high-concentration organic matrices.Five transformation products with lower antibacterial activity than kanamycin were identified using UPLC-QTOF-MS analysis.More importantly,hydrothermal treatment could remove 97.9％ of antibacterial activity (kanamycin vQ,1,109 mg/L) from actual production wastewater with CODcr around 100,000 mg/L.Furthermore,the methane production yield in anaerobic inhibition tests could be increased about 2.3 times by adopting the hydrothermal pretreatment.Therefore,it is concluded that hydrothermal treatment as a pretreatment technology is an efficient method for removing high-concentration hard-to-hydrolyze antibiotic residues from wastewater with high-concentration organic matrices.