Objective To determine the related substances in telmisartan and amlodipine tablets by HPLC. Methods The determination of telmisartan was performed on a capcell Pak C_(18) column(4.6 mmx150 mm,5 μm). The mobile phase consisted of 0.2% potassium dihydrogen phosphate and 0.38% sodium pentanesulfonate monohydrate solution(diluting phosphoric acid to pH 3.0) and acetonitrile-methanol(4:1), with linear gradient elution and the flow rate of 1.0 mL·min∼(-1). The detection wavelength was 230 nm. The determination of amlodipine was performed on an Xtimate C_(18) column, The mobile phase consisted of methanol-acetonitrile-0.7% triethylamine(35:15:50), the flow rate was 1.0 mL·min∼(-1), and the detection wavelength was 237 nm. Results Related substances were completely separated from the main constituents. The limit of detection of telmisartan was 0.5 ng and the limit of quantification was 1.8 ng, and the sample solution was stable at room temperature within 24 h. The limit of detection of amlodipine and impurity I was 0.30 ng and 0.58 ng, while the limit of quantification was 0.97 ng and 1.96 ng. The recovery of impurity I was 101.1%-104.1% with RSD less than 2%(n = 3). The sample solution was stable at room temperature within 24 h. Conclusion The method can be used for the quality control of telmisartan and amlodipine tablets.