A reliable, sensitive and selective method was successfully developed to determine 15 different mycotoxins simultaneously in foods and feeds. In this method, the homogenized sample was first treated with gel permeation chromatography (GPC) to eliminate most of coextracts, such as pigments, lipids and waxes. A quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was then carried out as a further cleaned up step, during which the polar interfering compounds such as organic acids and sugars were removed by vortexing with ODS in acetonitrile phase. Using double sample injection method, the analytes were separated by ZORBAX Eclipse plus C18 (1.8 µm, 2.1×100 mm) and detected by a MS/MS system with electrospray ionization (ESI) at multi-reaction monitoring (MRM) mode. The result indicated that the LOD of 15 mycotoxins were ranged from 0.07~5.0 µg/kg. Meanwhile, high correlation coefficients (r 2 >0.996) of 15 mycotoxins were obtained within their respective linear ranges. The average recoveries for lower, intermediate, and high spiked levels ranged from 80.1%~95.5% in company with RSD ranged from 10.5%~19.6%. The method not only represents many advantages including simple pre-treatment, good purification and high sensitivity, but also successfully fit the minimum limiting level requests from various countries including EU, USA and Japan.