A high performance liquid chromatography (HPLC) coupled to electrospray ionisation tandem mass spectrometry (MS/MS) method was described for the residue detection of chrysoidine in yellow-fin tuna in the present study. Samples were cleaned up with solid phase extraction (SPE) cartridge, and then injected into HPLC for separation. Multiple-reaction monitoring (MRM) was applied for quantitative determination. Results showed that the low limit of detection (LOD) of the method was 1.25×10 −12 g, and the low limit of quantification (LOQ) was 0.42μg/L. The standard calibration curve was y=2333.9x−845 (r 2 >0.99) with the linear range of 0.63–100μg/L. The average recoveries of chrysoidine ranged from 86.0% to 108.0% when the spiked concentration was from 0.5μg/kg to 20μg/kg. And the developed method also showed the good test precisions (RSD%: 4.38–14.27%).