In order to quickly determine three types of prohibited and restricted sedatives in fish, a rapid high performance liquid chromatography-tandem mass spectrometry method was explored for the simultaneous determination of three types of cocaine, one type of non-barbiturates, and six types of benzodiazepine tranquilizers in fish samples. The sample was extracted with acetonitrile, rapidly purified by low-temperature high-speed centrifugation, fast separated by ultra-performance liquid chromatography, and detected by online-coupled triple quadrupole/composite linear ion trap mass spectrometer. The linear working curves were measured in the concentration range of 0.2 to 20.0 μg/L, with linear correlation coefficients all higher than 0.999 0, and quantification limits at 1.0 μg/kg in fish. The recovery was measured by spiking 10 tranquilizer standards into carp muscle tissue at three levels of 1.0, 2.0 and 5.0 μg/kg, giving averaged data all within the range between 86.5% and 118.5%, with relative standard deviations between 2.2% and 7.7%. The method is validated to be simple, rapid, efficient, sensitive and accurate, being usable as a routine method for the determination of 10 types of tranquilizers in aquatic products.