A new method was established to determine Dicyandiamide in milk powder samples by QuEChERS cleanup combined with ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The sample was dissolved and extracted in hot water through ultrasonic wave, and protein was precipitated in acetonitrile. Then the extracted solution was purified by N-hexane and QuEChERS, and analyzed using UPLC-MS/MS. Dicyandiamide was identified by retention time and the ratio of the characteristic ions, and quantitatived with external standard method. In the study, the test situation and matrix effects of different samples matrix, including skimmed milk powder, whole milk powder, formula milk powder, acid milk powder and whey powder, were investigated. The result showed that the method quantitation limit (S/N=10) of dicyandiamide were 25 μg/kg in sample of formula milk powder and 12 μg/kg in the rest 4 kinds of sample. The average recoveries were between 88.6% and 111% at spiked levels of 12 - 250 μg/kg, the precision (n=6) ranged from 3.1% to 8.2%. The inter-day RSDs (n=5) were between 3.7% and 9.4%. Among 25 samples analyzed, only 2 samples were positive. The method was simple, sensitive, and accurate for the determination of dicyandiamide in milk powder samples.