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Salt-tolerant aerobic granular sludge(AGS) was successfully cultivated under the dual stress of tetracycline and 2.5% salinity, resulting in an average particle size of 435.0 ± 0.5 and exhibiting a chemical oxygen demand(COD) removal rate exceeding 80%, as well as excellent sedimentation performance. The analysis of metagenomics technology revealed a significant pattern of succession in the development of AGS. The proportion of Oleiagrimonas , a type of salt-tolerant bacteria, exhibited a gradual increase and reached 38.07% after 42 days, which indicated that an AGS system based on moderate halophilic bacteria was successfully constructed. The expression levels of targeted genes were found to be reduced across the entire AGS process and formation, as evidenced by qPCR analysis. The presence of int1 (7.67 log10 gene copies g -1 in 0 d sludge sample) enabled microbes to horizontally transfer ARGs genes along the AGS formation under the double pressure of TC and 2.5% salinity. These findings will enhance our understanding of ARG profiles and the development in AGS under tetracycline pressure, providing a foundation for guiding the use of AGS to treat hypersaline pharmaceutical wastewater.