Abstract: A method for the simultaneous determination of 21 mycotoxins in milk and dairy products using ultra performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry technology was established. After the milk and dairy products were extracted with acidified acetonitrile, they were purified by a Captiva-EMR Lipid purification column and chromatographically separated by a C₁₈ column. The mass spectrometry adopt full scan data-dependent MS/MS acquisition mode (Full MS/ddMS²) detected in positive and negative ion modes, and quantified by external standard method. The 21 mycotoxins all had a good linear relationship within a certain concentration range, the correlation coefficients (r) were greater than 0.99, the limits of quantification were 1.0~93.8 μg/kg, and the average recoveries of all mycotoxins were 60.3%~107.0% at three different levels, and the relative standard deviations (RSD) ranged between 0.4%~14.4%. This method was used to detect commercially available powdered and liquid milk and dairy products. Aflatoxin B₂ was detected in a fruit-added yogurt sample. The method was fast, accurate, suitable for the rapid determination of multiple mycotoxins in milk and dairy products, which could be used for efficient screening of mycotoxins risks.