Objective To explore the dynamic process of fluid-structure interaction (FSI) between venous blood and valves and the physiological mechanism that guarantees unidirectional blood reflux back to the heart. Methods A three-dimensional (3D) numerical model of the venous system was established using the immersed boundary/finite element method. In the simulation, information from medical images of human lower-extremity veins and the anatomical structure and size of the bovine great saphenous vein were applied. Moreover, a hyperelastic constitutive model was used to describe the incompressible, nonlinear, and hyperelastic mechanical responses of the venous valve under physiological conditions. Results The simulations visualized the process of venous blood transport and the function of venous valves in preventing reflux. The periodic characteristics of venous valve motion and blood flow were reproduced, and important physiological data during the entire cardiac cycle were discussed and quantified, including the pressure, velocity, and flow rate of venous blood; opening area of the venous valve; and stress and strain distributions on the valve surface. Conclusions The 3D FSI model numerically reproduces the physiological dynamic process within veins and potentially provides important references and guidance for revealing the pathological mechanism of venous diseases.