Abstract: Yi Dagen was a famous physician of Xujiang School in Ming Dynasty. In the process of syndrome differentiation and treatment, Yi Dagen attached great importance to pulse diagnosis and paid attention to the influence of time factors. His theory was based on "Yin and Yang having time rules and coordinating with pulse" in Basic Questions: The subtlety of pulse diagnosis, emphasizing the mutual reference of pulse and time, reflecting the fundamental principle of "correspondence between nature and man" in traditional Chinese medicine. The thought of mutual reference of pulse and time is mainly reflected in two levels: one is to guide syndrome differentiation, which can be summarized as referring to midnight-midday ebb flow to identify the location of the disease, referring to the four-season and five-viscus pulse method to identify the cause of the disease, referring to the north-south governance to identify the nature of the disease, and choosing the time to diagnose the pulse to identify the disease situation; the second is the whole process of syndrome differentiation and treatment, including pulse and time diagnosis and treatment according to the time. The idea of mutual reference of pulse and time plays an important guiding role in current clinical work. In the future, wearable pulse diagnosis equipment and intelligent monitoring technology can be combined to build a dynamic pulse analysis system to realize the real-time and precise application of the "mutual reference of pulse and time" theory.