For the treatment and prevention of animal diseases, antibiotics are commonly used in livestock and poultry farming. The large amount of antibiotics remaining in livestock and poultry manure brings a huge potential risk of the spread of antibiotic resistance genes. In order to further understand the degradation characteristics of typical antibiotics in livestock and poultry manure by hydrothermal pretreatment and anaerobic digestion, and clarify the correlation between antibiotics and methane production performance, pig manure was taken as the research object. The reduction effects of different temperatures (70℃, 90℃, 120℃, 150℃ and 170℃) by hydrothermal pretreatment on sulfadiazine, oxytetracycline and enrofloxacin were investigated. The degradation laws of sulfadiazine, oxytetracycline and enrofloxacin during mesophilic anaerobic digestion and their effects on methane production performance were studied. The results showed that the hydrothermal pretreatment had obvious reduction effect on the three antibiotics. Sulfadiazine and enrofloxacin were 100% removed by hydrothermal treatment at 70℃, while oxytetracycline was 100% removed by hydrothermal treatment at 90℃. During mesophilic anaerobic digestion, the removal rates of the three antibiotics were increased gradually with the prolongation of anaerobic digestion time. After 5d of anaerobic digestion, enrofloxacin basically reached 100% removal, while the removal rates of oxytetracycline and sulfadiazine were 39.76% and 21.29%, respectively. After 15d of anaerobic digestion, oxytetracycline basically reached 100% removal, while after 30d of sulfadiazine, the removal rate reached 52.9%. The degradation characteristics of the three antibiotics were quite different in the process of anaerobic digestion, but there was no significant difference in the biogas and methane production of pig manure with different antibiotics (P>0.05). In addition, when the sulfadiazine in pig manure was in the range of 5~150mg/kg, cumulative biogas and methane production from anaerobic digestion was negatively linearly correlated with sulfadiazine concentration (R2=0.9546 and R2=0.8654). However, there was no significant difference in biogas and methane production with different antibiotics (P>0.05). Therefore, hydrothermal pretreatment and anaerobic digestion can significantly reduce sulfadiazine, oxytetracycline, and enrofloxacin in pig manure, which can provide data support for the subsequent study of hydrothermal pretreatment combined with anaerobic digestion in the treatment of antibiotic-containing manure.