In traditional Chinese medicine, rules of Li-Fa-Fang-Yao is of critical importance in clinical practices. Li-Fa-Fang-Yao, which means principles, methods, formulae, and Chinese herbal medicines respectively, indicate the four basic steps of diagnosis and treatment: determining the cause, mechanism and location of the disease according to the medical theories and principles, then deciding the treatment principle and method, and finally selecting a formula as well as proper Chinese herbal medicines. In this paper, focused on major depressive disorder, we explored the rules of Li-Fa-Fang-Yao within the framework of traditional Chinese medicine. Through calculation, three clusters of Li-Fa-Fang-Yao on major depressive disorder were found based on the syndrome differentiation. What's more, these three clusters can also be validated by textbooks of traditional Chinese medicine.