Citric acid was reacted in concentrated sulfuric acid to product acetone- dicarboxylic acid. Methyl tetraester of ranelic acid was produced from acetonedicarboxylic acid by esterification reaction, cyclization reaction and alkylation reaction. Finally, strontium ranelate was synthesized from methyl tetraester of ranelic acid by hydrolysis reaction and salt formation. Orthogonal experiments and single factor experiments were developed to deter- mine the optimal conditions. The yield of the process is 37.9%. All compounds were con- firmed by H1-NMR, elemental analysis and XRD.