OBJECTIVE: To establish a method for the simultaneous determination of 6 kinds of residual organic solvents in Omeprazole magnesium, such as methanol, isopropanol, acetonitrile,dichloromethane, ethyl acetate and toluenein. METHODS: Headspace GC was adopted. The determination was performed on the column of DB-624 column by temperature programming. The inlet temperature was 200 ℃, and hydrogen flame ionization detector was adopted with the temperature of 250 ℃; nitrogen gas was used as carrier gas with flow rate of 2.0 mL/min; the splitting-radio was 5 ∶ 1, and sample size was 1 mL; the headspace temperature was 80 ℃ and the equilibrium time was 20 min. RESULTS: The linear range were 12.56-628.00 μg/mL for methanol (r=0.999 7), 20.22-1011.20 μg/mL for isopropanol (r=0.999 9), 1.96-97.76 μg/mL for acetonitrile (r=0.999 7),3.10-154.88 μg/mL for dichloromethane (r=0.999 8),20.69-1034.56 μg/mL for ethyl acetate (r=0.999 8), and 3.53-176.72 μg/mL for toluene (r=0.999 8); the limits of quantitation were 1.00, 0.91, 0.47, 0.93, 0.41 and 0.35 μg/mL respectively; the limits of detection were 0.31, 0.30, 0.14, 0.31, 0.12 and 0.11 μg/mL respectively; RSDs of precision, stability and reproducibility tests were lower than 3%; the recoveries were 94.53%-101.29% (RSD=2.15%,n=9), 97.78%-103.42% (RSD=1.77%,n=9), 96.99%-105.76% (RSD=2.59%,n=9), 96.83%-102.05% (RSD=1.86%,n=9), 97.98%-101.13%(RSD=0.88%,n=9) and 97.80%-102.40% (RSD=1.41%,n=9). CONCLUSIONS: The method is sensitive and accurate, can be used for the simultaneous determination of 6 kinds of residual organic solvents in Omeprazole magnesium, such as methanol, isopropanol, acetonitrile, dichloromethane, ethyl acetate and toluenein.