The river water-groundwater interaction zone is an important area for the enrichment, degradation, and transformation of pollutants and other biogeochemical processes. The distribution characteristics of antibiotics, as organic pollutants of wide concern, in the interaction zone is essential for understanding the migration and transformation process of pollutants in the environment. Due to the sensitive changes in the redox conditions and special composition of sediments in the interaction zone, this study established an effective pretreatment method for extracting 22 antibiotics and four sulfonamide metabolites in the interaction zone, and optimized the initial state of the samples, extraction temperature, pH value of the extraction solution and organic extraction solvent. The content of antibiotics in the sediments of the river water-groundwater interaction zone and lower reaches of the Hanjiang River was also analyzed. The results show that the best recovery of the target compounds is obtained by using pH 3 acetonitrile/Na2EDTA-Mcllvaine buffer(1:1, volume ratio) to digest and extract the unoxidized sediment samples at 40℃ three times using a microwave. A total of 11 antibiotics are detected in the sediments of the interaction zone in the lower reaches of the Hanjiang River, among which oxytetracycline and ofloxacin are the main compounds with the highest concentrations of 6.77 ng·g-1 and 5.81 ng·g-1, respectively. The vertical distribution of antibiotics in different sediment profiles is significantly different, which may be related to the lithology of sediments, physicochemical properties of antibiotics, and interaction between surface water and groundwater.