A highly efficient liquid chromatography/tandem mass spectrometric method was devised to quantify Sorafenib in human plasma with rapidity and sensitivity. The samples underwent extraction using the solid-phase extraction technique, employing a pretreatment solution of 100mM ammonium formate along with Sorafenib 13CD3 as the internal standard. Separation was carried out on a Phenomenex C18 column (50X4.6mm, 5μm) using a mobile phase composed of 10mM ammonium formate, methanol, and acetonitrile in the ratio of 20:5:75 (v/v/v) at a flow rate of 0.8 ml/min. Mass detection utilized the Turbo ion spray interface in positive ion multiple reaction monitoring mode (MRM), monitoring the ion transitions from m/z 465.1→252.1 (sorafenib) and 469.1→256.1 (sorafenib 13CD3, ISD). The calibration curves exhibited linearity within the range of 5-5000 ng/ml. The method demonstrated acceptable results for linearity, accuracy, precision, recovery, and matrix effect, with accuracy falling between 99.1% and 108.9%. The method precision showed a coefficient of variation (% CV) less than 2.4%.