A novel electroanalytical method has been developed for the quantification of hydrophobic lapatinib in the presence of non-ionic surfactant Triton X-100 on a glassy carbon electrode. Lapatinib presented three well-defined anodic peaks (Ep (1), Ep (2), and Ep (3)) by square wave voltammetry. The oxidation behavior of Ep (1) and Ep (2) showed diffusion-adsorption mix controlled processes by cyclic voltammetry. The possible electro-oxidation mechanism is discussed. The stripping conditions and square wave voltammetry parameters were optimized. The sensitivity of the proposed method was increased in the presence of Triton X-100. The hydrophobic interaction between Triton-X-100 and lapatinib guaranteed that more drug molecules could rapidly reach the electrode surface. The adsorptive stripping square wave voltammetry exhibits a linear calibration range from 2.0 x 10(-8) to 1.0 x 10(-6) mol l(-1) for both ip (1) and ip (2) in 0.1 M H2SO4. The developed method was applied for the quantification of lapatinib in serum sample and pharmaceutical dosage form with satisfactory accuracy and precision. In the serum sample, the values of LOD were found to be 5.71 x 10(-9) and 2.79 x 10(-9) mol l(-1) for ip (1) and ip (2), respectively. The developed method shows excellent analytical performance with nano-level detection limits, simplicity, and green chemistry compatibility.