Abstract: In order to monitor the residual contents of harmful organic solvents in leather and leather products, a method of gas chromatography-tandem mass spectrometry (GC/MS-MS) was established for the simultaneous determination of 21 harmful organic solvents. Residual harmful organic solvents in leather and leather products were ultrasonically extracted using ethyl acetate as the extraction solvent, then the extract was purified by solid-phase extraction (SPE) column and was analyzed by GC-MS/MS. All the analyte were calibrated by the external method. The results show that the limits of quantification (LOQ) are 15 μg/kg for ethylene glycol diethyl ether (EGEE), ethylene glycol dibutyl ether (EGDBE) and N-methylpyrrolidone (NMP); the limit of quantification is 20 μg/kg for ethylene glycol methyl ether (EGME); the limits of quantification are 25 μg/kg for diethylene glycol dimethyl ether (DEGDME), N,N-dimethylformamide (DMF), ethylene glycol butyl ether (EGBE), N,N-dimethylacetamide (DMA), N-methylformamide (MF) and diethylene glycol butyl ether (DEGBE); the limits of quantification are 50 μg/kg for ethylene glycol dimethyl ether (EGDME), ethylene glycol ethyl ether (EGEE), diethylene glycol methyl ether (DEGME), diethylene glycol ethyl ether (DEGEE), N-methylacetamide (MA), triethylene glycol dimethyl ether (TEGDME), formamide, triethylene glycol methyl ether (TEGME), triethylene glycol ethyl ether (TEGEE) and triethylene glycol butyl ether (TEGBE); the limit of quantification is 100 μg/kg for diethylene glycol diethyl ether (DEGDEE). The spiked average recoveries are 80.6%-95.8% under three different spiked levels. The relative standard deviation (RSD) of precision experiment changes from 2.3% to 6.7%. By using this method, 512 commercially available leather and leather product samples were detected and 9 target compounds such as DMF, DMA, EGEE, EGBE, DEGEE, DEGBE, TEGME, TEGBE and NMP were found to exist in 55 samples. The ratios of detection of DEGBE and DMF are the highest among these 9 target compounds. DEGBE is found to exist in 39 samples and DMF is found to exist in 30 samples. And the residual content of DEGBE is the highest, which reaches to 447.4 mg/kg. The method is simple, rapid and sensitive, which suits for determination of 21 harmful organic solvents in leather and leather products.