Abstract: To expand the application of novel nanomaterial based solid phase extraction technology in complex food matrices, a sulfonic acid based covalent organic framework (TpPa-SO₃H) was prepared as solid phase extraction adsorbents for the rapid analysis of three fluoroquinolones (FQs) antibiotics in milk by using high performance liquid chromatography (HPLC). TpPa-SO₃H was rapidly prepared by mechanical grinding, and its merits as novel solid phase adsorbents with high efficiency were fully explored in the detection towards FQs antibiotics. The effect of adsorbent dosage, pH of sample solution, adsorption time and desorption conditions were investigated to determine the effect of nanomaterial structure and properties on the solid phase extraction efficiency and the reproducibility with quantitative analysis capacity of this method. The results showed that TpPa-SO₃H possessed large specific surface area and abundant sulfonic acid functional sites, which could combine with FQs antibiotics efficiently and selectively. Under optimal operation conditions, the extraction recovery of three FQs antibiotic were in the range of 94.23%～98.68% within 4.0 min, which was significantly better than the national standard method. Thus a new high performance liquid chromatography (HPLC) method for the rapid analysis of FQs antibiotics in milk was established based on TpPa-SO₃H solid phase extraction, and the method owned the advantages of high sensitivity, excellent anti-interference ability, good repeatability, simplicity and rapidity. The detection limit of the three FQs antibiotics were in the range of 0.002～0.004 mg/kg, indicating that the method could be used for the detection of ultra-trace FQs antibiotics in real samples. In conclusion, the solid phase extraction combined with HPLC based on TpPa-SO₃H has realized the rapid detection of trace FQs antibiotics in milk with high sensitivity and selectivity, which indicating its great potential in scientific research and practical application.