Furmonertinib (AST2818) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) being developed for the treatment of patients with EGFR mutation-positive non-small cell lung cancer. Quantification of furmonertinib in plasma and cerebrospinal fluid (CSF) can be used to assess penetration of furmonertinib into the central nervous system (CNS). This paper described ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods for quantification of furmonertinib in human plasma and CSF. Sample separation was achieved on a Kinetex C18 column (100 mm x 2.1 mm, 2.6 mu m) after simple protein precipitation with acetonitrile. The mobile phase was composed of acetonitrile and 5 mM ammonium acetate with 0.2 % formic acid in water. Quantitative ion pairs were m/z 569.3 -* 72.2 for furmonertinib and m/z 526.5 -* 72.2 for aumolertinib, which was used as the internal standard (IS). The calibration curves showed good linearity (r(2 )> 0.99) over concentration range of 0.5-200 ng/mL(plasma sample) and 0.05-30 ng/mL(CSF sample). The precision (RSD) was <= 7.86 %, and the accuracy fell within the range of 96.2 %-109.3 %, all meeting acceptance criteria. The matrix effect was from 94.3 % to 102.1 %. The recovery of analytes fell within the range of 93.3 %-98.9 %. The established analytical methods showed great sensitivity, simplicity, accuracy and reliability for the analysis of furmonertinib in human plasma and CSF. This assay would be helpful to predict the effectiveness and toxicities of furmonertinib in the pursuit of precision medicine for lung cancer patients.