The invention discloses a method for detecting 2,2,6,6-tetramethylpiperidinooxy with high performance liquid chromatography-mass spectrometry. The method comprises the steps that 1, a test solution and a reference stock solution is prepared; 2, the test solution and the reference stock solution with a certain concentration gradient are subjected to sample introduction, a high performance liquid chromatograph mass spectrometer is used for detecting and recording a chromatogram; and 3, linear regression analysis is performed on the mass concentration of the reference stock solution and chromatogram peak area, a regression equation and correlation coefficients are obtained, and a standard curve is manufactured; and the peak area of 2,2,6,6-tetramethylpiperidinooxy in the chromatogram of the test solution is utilized to calculate the content of 2,2,6,6-tetramethylpiperidinooxy by an external standard method. The method provided by the invention is the first method for detecting 2,2,6,6-tetramethylpiperidinooxy developed in the field. The method has accurate detection result, high sensitivity, good stability, and low detection limit, and totally meets detection requirements for genotoxic impurities in the field.