Little is currently known about the alterations in the topological organization of the white matter (WM) structural networks in patients with multiple sclerosis (MS). In the present study, we used diffusion tensor imaging and deterministic tractography to map the WM structural networks in 39 MS patients and 39 age-and gender-matched healthy controls. Graph theoretical methods were applied to investigate alterations in the network efficiency in these patients. The MS patients and the controls exhibited efficient small-world properties in their WM structural networks. However, the global and local network efficiencies were significantly decreased in the MS patients compared with the controls, with the most pronounced changes observed in the sensorimotor, visual, default-mode, and language areas. Furthermore, the decreased network efficiencies were significantly correlated with the expanded disability status scale scores, the disease durations, and the total WM lesion loads. Together, the results suggest a disrupted integrity in the large-scale brain systems in MS, thus providing new insights into the understanding of MS connectome. Our data also suggest that a topology-based brain network analysis can provide potential biomarkers for disease diagnosis and for monitoring the progression and treatment effects for patients with MS.