Semicarbazide (SEM), a metabolite of nitrofurazone (NFZ), is widely used to detect the illegal application of NFZ in crustaceans. The conventional detection method involves chemical derivatization combined with reversed-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS), which is both complex and time-consuming. To address this limitation, a more efficient approach was developed for SEM detection. This study introduces a modified QuEChERS pretreatment method coupled with hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) for detecting SEM in crustaceans. The proposed method is simple, fast, and highly accurate, making it universally applicable for SEM detection in crustaceans. Additionally, the method was applied to investigate NFZ metabolism in