OBJECTIVE: To establish a method for the simultaneous contents determination of chloramphenicol and diphenhydramine hydrochloride in Chlorobenzene alcohol solution. METHODS: HPLC was performed on the column of Diamonsil C with mobile phase of phosphate buffer-acetonitrile (66.5 ∶ 33.5,V/V) containing 0.01 mol/L sodium heptane, column temperature was 35 ℃, flow rate was 1 ml/min, detection wavelength was 258 nm for diphenhydramine hydrochloride and 277 nm for chloramphenicol, the injection volume was 10 μl. RESULTS: The linear range was 34.8-139.4 μg/ml for chloramphenicol (r=0.999 8) and 93.0-930.5 μg/ml for diphenhydramine hydrochloride (r=0.999 8); RSDs of precision, stability and reproducibility tests were lower than 2.0%; recoveries were 97.70%-104.02% (RSD=2.2%,n=9) and 96.72%-101.72%(RSD=1.6%,n=9). CONCLUSIONS: The method is specific, accurate with good precision, and suitable for the quality control of Chlorobenzene alcohol solution.