An Ultra-High Performance Liquid Chromatography-Quadrupole/Electrostatic Field Orbitrap High-resolution Mass Spectrometry method （UPLC-Q-Orbitrap HRMS）has been developed for the determinations of the drug residues of 21 SAs and 12 QNs in aquatic products.The sample was extracted by acetonitrile, cleaned up by acetonitrile saturated normal hexane and quantified in internal standard method.The results showed that 33 products presented a good linear relation in the range of 0.1～100 ng/mL. r²＞0.996. The limits for qualitative detection was 2 μg/kg. The average recoveries at three spike levels ranged were 54.3%～120.4%, with RSDs ranging 1.7%～11.9%. The developed method was easy operation high sensitivity, which can meet the requirements of daily inspection.