Novel C18-functionalized magnetic nanomaterials; i.e., C18@poly-styrene-divinylbenzene-glycidyl methacrylate-Fe3O4 (C18@PS-DVB-GMA-Fe3O4) have been synthesized by using N, N-dimethyloctadecylamine as modifying agent, which could be beneficial to remove the blood phospholipids. The C18@PS-DVB-GMA-Fe3O4 nanoparticles have been used and evaluated in the Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) procedure for human plasma prior to the analysis of propofol by supercritical fluid chromatography (SFC). In the QuEChERS procedure, human plasma samples are directly mixed with extraction solvent and C18@PS-DVB-GMA-Fe3O4 nanoparticles, and the extraction and cleanup procedures have been accomplished simultaneously. The SFC separation was performed with a C18 column (Thermo Scientific™ Acclaim™ 120, 250 × 4. 6mm, 5μm) within 5min, using thymol as the internal standard. Supercritical carbon dioxide was used as the mobile phase with methanol as the cosolvent at the flow rate of 1.0mL/min. The column temperature was 38°C, and detection wavelength was 275nm. A good linearity was obtained among the propofol concentration range of 0.5-10mg/L (R2 = 0.9997) with the limit of detection of 0.17mg/L. Recoveries were in the range of 76.5-91.9%, with RSD less than 7.9%. These results suggested that method is convenient, rapid with high accuracy and little matrix effect, and suitable for rapid determination of propofol plasma concentration.