The aim is to establish a method for the content determination of clonidine hydrochloride in Zhenju Jiangya(ZJ) tablets by solid phase extraction and high performance liquid chromatog.(SPE-HPLC). Samples were pretreated by Cleanert SCX-SPE cation solid phase extraction column and analyzed by HPLC consisting of a Agilent ZORBAX SB-C18 column(4.6 mm*250 mm, 5μm) and a mixture of acetonitrile -0.05% H3PO4(10:90) solution as mobile phase. The column temperature was 30°C, flow rate was 1.0 mL/min and wavelength was 220 nm. The determination of clonidine hydrochloride in ZJ tablets had the regression equation as y=2.9662x+0.0485(r=0.99999), which showed good linearity in the range of 1.234-123.4 ng. The average recovery of high, medium and low doses was 98.56% and RSD of recovery was 0.68%. This method had good repeatability, intermediate precision and accuracy, and met the requirement of content determination method. This method could effectively eliminate the neg. interference with good specificity, sensitivity, reproducibility and accuracy, and could be used as a reliable tech. method to analyze clonidine hydrochloride in ZJ tablets.