An orthogonal-design experiment with the type of L9(34) is applied to optimize the condition for sulfonation of andrographolide with concentrated sulfuric acid.The optimal sulfonation condition is established by general analysis of reacting percentage of sulfonation agent and the yield of main aim product with multi-target grading method.The multi-target grade is significantly affected by the weight ratio of concentrated sulfuric acid to andrographolide,whereas reaction time and concentration of the alkali used for neutralization have insignificant effect.The optimal condition is established as concentrated sulfuric acid reacting with half weight of andrographolide for 72 h and then neutralized by sodium hydroxide with a weight concentration of 30%.