Abstract: Extraction of sediment samples was carried out with an ultrasonic method using a mixture of acetonitrile and citric buffer as the extraction solution. The extracts of the solid samples were then cleanedup and enriched with a tandem solid phase extraction (SPE) method, followed by an analysis using rapid resolution liquid chromatography-tandem mass spectrometry (RRLC-MS/MS). A study of the occurrence and special distribution of 41 antibiotics from 13 sampling sites in sediments of Guangzhou section of the Pearl River was conducted. The results showed that 24 antibiotics were detected in the sediments of Guangzhou section of the Pearl River in dry and wet season. The concentrations in dry season and wet season were at the range of ND (not detected)~54.800 g/g and ND~3.433 g/g respectively, and the antibiotics of the highest content in the two seasons were both oxytetracycline. In sediments, the predominant antibiotics were fluoroquinolones and tetracycline antibiotics. The total antibiotic concentration in dry season was higher than that in wet season. The spatial distribution of antibiotics in the sediments of Guangzhou section of the Pearl River followed the order: streams in densely populated urban area the river reaches in densely populated urban area middle and lower reaches of the river the upstream of the river, which is basically the same as the distribution of pollution and sewage in the urban area of Guangzhou.