The presence of high level of antibiotics in the antibiotic fermentation residue is one of the main reasons that prevent their direct disposal or further use as a resource. In this study, the feasibility of using the hydrothermal pretreatment for removing oxytetracycline (OTC) from its fermentation residue and enhancing anaerobic digestion was evaluated under different temperatures i.e. 110, 130, 150 and 170°C. The results showed that the removal rate of OTC increased as a function of temperature, and hydrothermal treatment at 130°C for 5 min was found sufficient to reduce the concentration of OTC from 3.9 mg/g to less than the detection limit (i.e., 0.25 ng/g). Biochemical methane potential tests showed that the cumulative methane production over 23 d was 73.7, 215.9, 656.8, and 439.0NmL CH4/gVS for the raw residue and the residue treated at 130, 150, and 170°C for 5 min, respectively. At the same time, the abundances of tetracycline resistance genes were reduced by hydrothermal treatments followed by anaerobic digestion. Conclusively, it is suggested that hydrothermal treatment at 150°C for 5 min was found beneficial for OTC fermentation residues ensuring the removal of OTC and further use of the residue for anaerobic digestion.