Abstract: In the synthetic route towards tetrasulfonic acid dereivative of hypericin, self-condensation reaction of emodin anthrone was prompted by means of the microwave assisted organic synthesis. Three influencing factors of this step such as the microwave heating temperature, irradiation time and catalyst were studied and the resulting optimal conditions were determined as follows: 150°C, 1 h and no catalyst used. The yield of this step was increased by 82.2% with microwave assisted synthesis, and the total yield of the scaled-up synthesis of hypericin tetrasulfonic acid was achieved 65.3%. In comparison with conventional heating method, it is demonstrated that the use of the microwave method has enhanced the reaction efficiency and yield, reduced side-reactions and made the synthetic procedure more beneficial to low-carbon and environmental protection.