Objective Two different venous models, one with and one without a venous sinus, each containing two pairs of adjacent orthogonal venous valves, were constructed. Using fluid-structure interaction (FSI) simulations, the influence of the venous sinus structure on blood flow in the lower limb venous system was studied, and the role of the venous sinus structure in the process of venous valve opening and closing was analyzed. Methods Based on ultrasound images and anatomical images of animals, two distinct three-dimensional (3D) geometric models of the venous system were constructed using modeling software. Using the immersed boundary method, FSI simulations of venous valves were performed to obtain hemodynamic parameters, such as changes in valve morphology, flow streamlines distribution, wall shear stress (WSS) distribution, and Q-criterion intensity distribution. Results The geometric opening area of the valve in the model with sinuses was larger than that in the model without sinuses. The distribution of blood streamlines demonstrated the existence of vortices in the sinus region and helical flow within the vessel. The same venous valve pair exhibited an asymmetric distribution of WSS, with the region of high WSS behind the venous valve and the Q-criterion intensity between the far and near end valves being smaller in the sinus model compared to the non-sinus model. Conclusions The blood flow between two adjacent pairs of orthogonal venous valves exhibits a helical flow characteristics. The venous sinus structure facilitates the opening of the venous valve and the generation of vortices in the sinus region. However, the venous sinus structure may somewhat weaken the helical flow produced by the orthogonal venous valves. The venous sinus has a critical influence on the hemodynamics of the venous system, and in the study of venous valves, the venous sinus structure should be considered as an indispensable component.