Osimertinib (OSIM) is widely used as a mainstream drug for the treatment of non-small cell lung cancer (NSCLC). However, the lack of a rapid extraction and detection method for OSIM and its metabolite, AZ-5104, has limited clinical drug metabolism and drug resistance research because the drug is unstable. In this study, a new ionic liquid hybrid hierarchical porous material (IL-HHPM) was synthesized with hierarchical porous structures, including micropores (1.6-2.0 nm), mesopores (2.0-50.0 nm), macropores (50.0-148.7 nm), and multiple functional groups via a one-step hydrothermal method using silanized ionic liquids (IL) as functionalized hybrid monomer. The IL-HHPM has the advantages of a high specific surface area (437.4 & PLUSMN; 4.6 m2 g-1), sizable pore volume (0.74 cm3 g-1), and fast mass transfer, additionally, the IL-HHPM adsorbed OSIM and AZ-5104 via & pi;-& pi; interactions and hydrogen bonding. OSIM and AZ-5104 were rapidly extracted and measured in human urine using rapid and miniaturized centrifugal spin-column extraction (MCSCE), which was based on the IL-HHPM. The optimized factors for the extraction recoveries of OSIM and AZ-5104 were adsorbent dosage (8.0 mg), sample volume (0.5 mL), and operation time (9.0 min), and markedly reduced the adsorbent dosage and operation time. The IL-HHPM-MCSCE-HPLC method displayed good linearity (0.02-5.00 & mu;g mL-1, r & GE; 0.9997), satisfying accuracy (spiked recoveries of 87.7%-100.0%), and good precision (RSDs & LE; 7.0%). The developed method is rapid, sensitive, and reproducible for the simultaneous determination of trace level of OSIM and AZ -5104 in human urine.