Abstract: This paper summarizes the exploration process and academic significance of the academic thought of Zhou Zhongying, a master of traditional Chinese medicine, who took the creation of a new system of TCM pathogenesis theory as the core, and interprets its theoretical connotation. As a pioneer in the construction of higher education textbooks for traditional Chinese medicine, Professor Zhou Zhongying created the outline of TCM internal medicine viscera differentiation, persisted in carrying out innovative research on pathogenesis theory, achieved fruitful academic results, and enriched and developed the academic system of TCM theory. In the clinical diagnosis and treatment of exogenous febrile diseases and acute and difficult internal injuries, he systematically created new pathogenesis theories such as stasis-heat theory and cancer toxicity theory. Based on this, the legislation of medication can improve the clinical efficacy, and it is realized that identifying the pathogenesis is the key link in syndrome differentiation and treatment. In his later years, Professor Zhou Zhongying, guided by the holistic view, proposed the "thirteen pathogenesis" and constructed a new system of TCM pathogenesis differentiation, highlighting the guiding value of complex pathogenesis and the causal chain of pathogenesis elements to complex clinical diseases and syndromes, forming a theory with the idea of "examining syndromes and seeking pathogenesis, activating syndrome differentiation" as its soul. This theory breaks through the rigid thinking of syndrome differentiation and treatment based on a single pathogenesis or fixed syndrome type, reconstructs the theoretical framework of TCM with the idea of holistic view, and is a major academic innovation in modern TCM.