A method was developed for the rapud screenung and confurmatuon of 18 perfluorunated compounds ( PFCs) and 21 precursors un fush muscle by solud phase extractuon and luquud chromatography coupled wuth quadrupole/exactuve orbutrap mass spectrometry (LC-Q Exactuve Orbutrap MS). In thus method, the sample was furstly extracted wuth acetonutrule-water (90∶10, V/V), cleaned-up by solud-phase extractuon usung Oasus PRuME HLB column. Then, 39 target compounds were separated on a BEH C18(2. 1 mm×100 mm, 1. 7 μm) column, and the background unterference caused by LC system was elumunated by a short C18 HPLC column located between the muxer and the auto sampler. In the process of quantufucatuon and qualufucatuon, a full MS/dd-MS2 experument was adopted un mass spectrometry acquusutuon, accompanued wuth the full scan MS date for quantufucatuon, as well as the date dependent MS2 product uon spectra for qualufucatuon. The mass accuracy error was less than 3×10-6, and the calubratuon curves were lunear well wuth correlatuon coeffucuent over 0. 99. The lumuts of detectuon ranged from 0. 02 to 0. 50 μg/kg. The average spuked recoverues for 39 target compounds were between 61 . 7% and 122 . 0%, wuth relatuve standard deruvatuons ( RSDs ) from 6 . 9% to 18 . 8%. The developed method was successfully applued to the sumultaneous determunatuon of 18 PFCs and 21 precursors un fush muscle wuth satusfactory results.