Abstract: To determine the maleic hydrazide residues in tobacco and tobacco products, an SPE-UPLC-MS/MS method was developed by adopting solid phase extraction cartridges (SPE) for sample clean-up and ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) for detection. Tobacco samples were extracted with hydrochloric acid under heating and refluxing, and further purified by solid-phase clean-up with graphitized carbon black (GCB) column. The ESI source in negative ion mode was used for qualitative and quantitative analyses under multiple reaction monitoring (MRM) mode with d²-maleic hydrazide as the internal standard. The results showed that:1) After the purification by GCB column, the pH value of the eluent was near neutral after removing hydrochloric acid. 2) The limit of quantification was 0.47 mg/kg, and recoveries ranged from 94.2% to 102.1% with relative standard deviation (RSD) less than 6%. 3) The maleic hydrazide residues in 13 tobacco samples were detected by this method and compared with those determined by the standard method described in YC/T 405.5-2011, the data using the two methods agreed with each other very well. This method is sensitive, stable, accurate and suitable for determining the maleic hydrazide residues in tobacco samples.