A simultaneous analytical method for the organophosphorus insecticide fenthion and its five metabolites (fenthion oxon, fenthion oxon sulfoxide, fenthion oxon sulfone, fenthion sulfoxide, and fenthion sulfone) was developed based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Five matrices (brown rice, chili pepper, orange, potato, and soybean) were selected to validate the method. The target compounds were analyzed using positive electrospray ionization in the multiple reaction monitoring mode. For the best sensitivity in regard to the detector response, water and methanol containing formic acid (0.1%) were selected as the mobile phase. The optimum extraction efficiency was obtained through a citrate-buffered QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. Recovery tests were carried out at three spiking levels (n = 3). At all fortification levels, the accuracy and precision results were between 70% and 120% with a relative standard deviation of ≤15%. The limit of quantitation was 0.01 mg/kg, and the correlation coefficients (r 2 ) of the matrix-matched calibration curves were >0.99. Significant signal suppression in the detector responses were observed for all matrices, suggesting that a compensation method, such as matrix-matched calibration, is required to provide accurate quantitative results. The applicability of the presented method was confirmed for the simultaneous analysis of fenthion and its metabolites in various crops.is a widely used insecticide belonging to the organophosphate group. As an inhibitor of acetylcholine esterase, fenthion has been used to control a wide range of pests, such as fruit flies, mosquitoes, mites, and aphids in a variety of crops [6]. Although fenthion exhibits moderate toxicity and is classified as toxicity Class II by the U.S. Environmental Protection Agency (EPA), the adverse effect of fenthion on the environment is a controversial issue due to the high toxicity on non-target birds, aquatic invertebrates, and honey bee [7]. Moreover, it has been reported that the acute and chronic dietary risks of fenthion exceed the concern level suggested by the EPA for the general U.S population [8]. The cumulative effect of fenthion caused by its high solubility in fat tissue could be considered another threat to human health. [9]. To protect human health, animals, and the environment, continuous risk mitigation measures ought to be taken to reduce any possible risks from fenthion exposure. However, due to its broad-spectrum applicability in agriculture, fenthion is often detected in a variety of foods and environments [10,11]. Therefore, a reliable analytical method for the determination of fenthion residues is necessary to evaluate food safety and possible risks to human health.The five degradation products, fenthion oxon, fenthion oxon sulfone, fenthion oxon sulfoxide, fenthion sulfone, and fenthion sulfoxide, are the major metabolites of fenthion, which are produced as the result of metabolism in animals, plants, and thei...