OBJECTIVE: To establish a method for simultaneous determination of matrine, linarin, berberine hydrochloride and osthole in Shenju lotion. METHODS: HPLC was performed on the column of Dionex C18 with mobile phase of acetonitrle - 0.1% triethylamine (pH was adjusted to 7.2 with phosphoric) (gradient elution) at a flow rate of 1.0 ml/min, detection wavelength was 210 nm, column temperature was 30 ℃, and injection volume was 20 μl. RESULTS: The linear range was 1.400-8.400 μg for matrine (r=0.999 4), 0.152-0.912 μg for linarin (r=0.999 6), 0.248-1.488 μg for berberine hydrochloride (r=0.999 9) and 0.128-0.768 μg for osthole (r=0.999 4); limit of quantitation was 84.85, 3.15, 15.03, 7.76 ng, limit of detection was 24.13, 0.89, 4.27, 2.20 ng; RSDs of precision, stability and reproducibility tests were lower than 2%; recoveries were 96.29%-99.06% (RSD=1.10%,n=9), 96.49%-98.27% (RSD=0.69%,n=9), 99.26%-101.13%(RSD=0.62%,n=9) and 96.27%-98.64% (RSD=0.89%,n=9). CONCLUSIONS: The method is simple, accurate and reproducible, and can be used for the simultaneous determination of matrine, linarin, berberine hydrochloride and osthole in Shenju lotion.