To establish a method for the simultaneous determination of 15 mycotoxins in grains by ultra performance liquid chromatography tandem mass spectrometry (UPLC/MSMS). Samples were extracted by acidified acetonitrile solution, purified by impurity adsorption column prime HLB, and compensated for matrix effect interference by adding stable isotope internal standard. Phenomenon Kinetex Bipheny l100A column was used as separation column, gradient elution, UPLC-MS/MS for detection and internal standard method for quantification. The results showed that the linear correlation coefficient of 15 mycotoxins was greater than 0.996, the detection limit was 0.2-15 μg/kg, the quantitative limit was 0.8- 30 μg/kg, the recovery of three levels of three kinds of matrixes was 76.9%-116.1% and the RSD was 1.4%- 10%. The certified reference materials of corn matrix were The results from test and verification of corn matrix reference materials showed that the detection values of 8 mycotoxins were in the marked range. This method has been used to detect 135 batches of food sold in the market, 97 batches of samples were detected have mycotoxin with a detection rate of 71%, multi toxin simultaneous pollution was common. The method is simple, rapid and reliable, and can be used for the rapid and accurate detection of 15 mycotoxins in grains.