OBJECTIVE： To establish a method for the determination of residual solvent of ethanol and toluene in diphenhydramine hydrochloride raw material. METHODS： Headspace capillary gas charmatography and butanone as internal standard were used. The column was Agilent DB-624 capillary column， inlet temperature was 200 ℃， hydrogen flame ionization detector was 250 ℃， the carried gas was high purity nitrogen， flow rate was 3.0 ml/min with temperature programmed， the splitting-ratio was 20 ∶ 1， the containers of headspace injector were in equilibrium at 80 ℃ for 30 min， and the injection time was 1 min. RESULTS： With this chromatographic condition， ethanol， toluene and internal standard peak were well separated； there was a good linear relationship of ethanol and toluene in the range of 0.02-0.8 mg/ml （r＝0.999 8 and r＝0.999 4）； RSDs of precision and stability test were lower than 3％； recoveries were 95.50％-103.50％（RSD＝2.6％，n＝9） and 96.91％-103.74％ （RSD＝2.2％，n＝9）. CONCLUSIONS： The method is simple， sensitive and accurate， and can be used for the determination of residual solvent of ethanol and toluene in diphenhydramine hydrochloride raw material.