A QuEChERS-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of auramine O, curcumin, deoxymethylcurcumin and dideoxymethylcurcumin in durian. The samples were extracted by 0.1% formic acid acetonitrile, purified by 100 mg C₁₈ and 100 mg anhydrous magnesium sulfate. Using 0.1% formic acid aqueous solution and 0.1% formic acid acetonitrile as mobile phase, the samples were separated by Poroshell 120 EC-C₁₈ column, monitored by multiple reaction monitoring in a positive ion mode, and quantitatively analyzed by an external standard method. The results showed that four compounds had good linear relationships in the mass concentration range, and the determination coefficient R² was > 0.999. The limits of detection and quantitation of auramine O were 0.4 μg/kg and 1.0 μg/kg, respectively. The limits of detection and quantification of curcumin, deoxymethylcurcumin and dideoxymethylcurcumin were 2.0 μg/kg and 5.0 μg/kg, respectively. The average recovery rates were 88.3%-109.3% and the relative standard deviations were 0.59%-8.93% at low, middle and high levels. The developed method is rapid, convenient, sensitive and accurate, and can be used for the determination of auramine O, curcumin, deoxymethylcurcumin and dideoxymethylcurcumin in durian.