In order to provide scientific basis for the engineering structure design and working condition control for the main tunnel system of a deep tunnel drainage system, numerical simulation was carried out combined with physical model test. A three-dimensional numerical model of the main tunnel system including two shafts and a connected main tunnel section was established, which had the same body structure as the physical model. A three-dimensional dynamic simulation of the inflow process was performed under two extreme large inflow conditions. The results show that the water intake process of the main tunnel system under large flows can be summarized into 4 stages, flow entering into the main tunnel from two shafts, flow colliding to form surface waves which are transmitted and superimposed in the main tunnel, lower and upper side tunnel ports blocked successively, and inflow stopped. The inflow mainly affects the seal degree of the port in the main tunnel system, the phenomenon of hysteretic gas and the process time of each inflow stage. The seal degree of the port in the main tunnel system and the phenomenon of hysteretic gas is more serious under larger inflow condition, and the process time of each inflow stage is substantially reduced.