Abstract: Perfluorinated compounds (PFCs) are extensively utilised in the petroleum industry. As a class of emerging contaminants, PFCs have the potential to enter the product chain during the refining process, which may lead to environmental pollution and endanger human health. However, efficient and reliable methods for the pretreatment and detection of PFCs in petroleum-based samples are still lacking. Therefore, an analytical method was developed in this study, combining ionic liquid (IL) extraction, solid-phase extraction (SPE) purification, and liquid chromatography tandem high-resolution mass spectrometry detection. Orthogonal experimental design was used to optimise the key pretreatment conditions. The optimised procedure yielded the following results: The sample was extracted with 0.25 mL of 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF₆). The extract was then diluted to 250 mL, adjusted to pH 5, and purified using a weak anion exchange SPE cartridge. The purified samples were separated on a C18 column and ionised by electrospray ionisation (ESI) in negative ion mode. Analysis was subsequently performed using an Orbitrap mass spectrometer in parallel reaction monitoring (PRM) mode. The limit of detection was as low as 0.014 ng/mL, and the limit of quantitation reached 0.059 ng/mL. The analytical method was applied to determine PFCs in crude oil and FCC tail oil. The detected concentrations ranged from 0.88×10⁻⁹–1.47×10⁻⁹ and 10.79×10⁻⁹–17.18×10⁻⁹, respectively, with recoveries ranging from 58% to 112%. The results demonstrated that the analytical method established in this study can effectively mitigate the matrix effect of petroleum samples, enable efficient enrichment and determination of PFCs, and is generally applicable to petroleum samples with diverse physicochemical properties.