Abstract: To investigate the residue behavior and dietary risks of fluopicolide and cymoxanil in melon, a rapid and accurate detection method using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the determination of the residue levels of these two pesticides in melon. The results showed that at the spiking levels of 0.020-2.0 mg/kg, the average recoveries of fluopicolide and cymoxanil were 83%-102% and 87%-99%, respectively, with the relative standard deviations (RSD) of ≤7.2%, and the limits of quantification were both 0.020 mg/kg, demonstrating good accuracy and repeatability. Residue dissipation trials demonstrated that the half-lives of the two pesticides were 3.8-5.3 days and <3 days, respectively, indicating rapid dissipation rates. The supervised field trials conducted in six representative regions revealed that the residues of fluopicolide in melons were <0.020-0.052 mg/kg and <0.020-0.048 mg/kg at 7 and 10 days after the last application, respectively, while residues of cymoxanil remained below 0.020 mg/kg at both sampling intervals. Dietary exposure risk assessment indicated that the contribution rates of fluopicolide and cymoxanil residues in melon to the risk quotient for different consumer groups were 0.0271%-0.0919% and 0.167%-0.566%, respectively, which were below the threshold of 1%. These results suggested that under normal dietary conditions, the chronic intake of fluopicolide and cymoxanil residues via melon consumption is unlikely to pose a significant health risk. The findings of this study not only provide a scientific basis for the rational use of fluopicolide and cymoxanil in melon, but also offer important data reference for establishing the maximum residue limits in China.