Abstract: Hydrothermal pretreatment (HTP) can be used to decompose the sulfadiazine (SDZ) during continuous anaerobic digestion (AD) of pig manure. This study aims to explore the effect of HTP on the SDZ degradation and performance of AD system. Pig manure with SDZ was taken as the research object. A comparison was made on the degradation regular, SDZ paths and products, as well as the gas production performance of pig manure with/without HTP during AD. The results showed that the HTP (150 °C) significantly increased the comprehensive removal rate of SDZ in the mesophilic continuous AD reactor (P <0.05), particularly from 40.5%~58.5% to 54.4%~75.2%. Moreover, the biodegradation paths of SDZ were inferred through intermediate degradation products, including SDZ hydrolysis, hydroxylation, thiodeoxidation, amino oxidation, nitroation, amidation and pyrimidine ring cleavage. HTP enhanced the degradation products and paths of SDZ, biodegrade SDZ from different degradation paths, and the removal rate of SDZ. There were four paths of degradation in pig manure with HTP, while there was only one degradation path without HTP. In terms of AD performance, the system was stabilized after 25 days, the daily gas production in the R0 reactor was stable at 5.14 L/d, and the cumulative VS gas production rate was 16.64 L/g; In the R0h reactor, the daily gas production was stable at 6.89 L/d, and the cumulative VS gas production rate was 22.31 L/g. The daily biogas yield of the reactor and the volume production rate increased by about 34.05% (P<0.05), and 34.00%, respectively, after stable operation with HTP. There was little difference in the methane content between the two reactors after two SRTs. The average contents of methane in R0 and R0h reactors were 61% and 59%, respectively. Thus, the AD process was stable in the two groups of reactors over the whole operation stage, according to the biogas production rate and methane content. The degradation of organic matter was also enhanced for the high concentration of VFAs after HTP. The substrate was provided for the subsequent stage of methane production, in which the acetic acid content accounted for 25.3%~46.1%. In addition, the microbial communities showed that Firmicutes and Bacteroidota were the dominant phylum bacteria in the reactors during anaerobic fermentation. Their relative abundance was beneficial to the degradation of antibiotics. A comparative analysis was also made on the microbial community at the class level. It was found that Clostridia and Bacteroidia were the main microorganisms in the two reactors. The relative abundance of Proteiniphilum increased after HTP. The full hydrolysis of pig manure was also realized for the better performance of methane production. Meanwhile, it was found that Syntrophomonas and Sedimentibacter were highly correlated with the degradation of SDZ, and the relative abundance of Sedimentibacter after HTP was significantly higher than that without HTP, indicating the better degradation of antibiotics. Therefore, the HTP coupled with the AD process can be expected to simultaneously improve the degradation of SDZ and AD performance, particularly for the ecological safety of biogas liquor.