OBJECTIVE To establish a determination method of the related substances of lapatinib ditosylate tablets by HPLC. METHODS Waters Xterra MS C₁₈ column (4.6 mm×250 mm， 5 μm) was selected； 0.01 mol·L^-1 sodium dihydrogen phosphate solution (pH adjusted to 3.2 with phosphoric acid) was mobile phase A， acetonitrile was mobile phase B， and gradient elution was used at a flow rate of 1.0 mL·min^-1. The detection wavelength was set at 265 nm， and the column temperature was 40 ℃. RESULTS Lapatinib Impurity A， LAPA-2 and LAPA-1 had good linearity in the range of 0.02-8.08， 0.02-8.26 and 0.02-8.29 mg·mL^-1， respectively (r ≥ 0.999 9). The limits of quantitation (LOQ) were 1.0， 1.4， and 2.1 ng， respectively. The average recovery (n=9) was in the range of 100.2%-102.9%， and RSDs (n=9) were in the range of 0.02%-0.66%. CONCLUSION The method is simple， accurate， and specific and can quantitatively determine the related substances of lapatinib ditosylate tablets.