Abstract: OBJECTIVE To develop an HPLC method for the determination of sorafenib in human plasma. METHODS The analytical column was packed with ZORBAX XDB-C₁₈(150 mm×4.6 mm, 5 mm). A mixture of acetonitrile-0.1% trifluoroacetic acid-water(49∶20∶31) was used as the mobile phase with the flow rate of 1.0 mL·min^-1. The detection wavelength was set at 266 nm. The column temperature was set at 35 ℃. The plasma was extracted with ethyl acetate under basic conditions, and itraconazole was used as internal standard. RESULTS Excellent liner relationship was obtained in the range of 0.05-10.00 mg·L^-1(r=0.999 7). The intra-day RSDs were 3.78％, 2.31％and 2.16％, and inter-day RSDs were 4.52％, 3.46％ and 2.14％, respectively at three concentrations(0.1, 2.50, 7.50 mg·L^-1). The method recoveries were (97.2±4.54)%, (100.8±2.51)%, and (100.2±2.17)%, respectively. The absolute recoveries were (80.55±4.13)％, (81.42±2.91)％, (82.07±1.62)%, respectively. CONCLUSION The method is simple, accurate and sutiable for sorafenib cliniacl therapeutic drug monitoring and its pharmacokinetics study.