To investigate the alterations of brain structural–functional connectome in two large samples of unilateral sudden sensorineural hearing loss (USSHL) patients within the acute period.The human brain is a large-scale integrated network (connectome) in the functional and structural domain. Current noninvasive multimodal imaging techniques and graph theoretical analysis have been able to provide a novel framework for analysing such complex networks and further characterize its topological properties and underlying mechanisms. Sudden sensorineural hearing loss is typically unilateral and considered to be an otologic emergency which can be associated with tinnitus and vertigo. While previous neuroimaging studies have uncovered alterations in several specific brain structural and functional networks in patients with USSHL, little is known about the changes in the relationship between structural and functional brain connectome. And how do functional brain networks emerge from structural brain connectivity in USSHL is still unknown.We constructed functional connectivity networks from partial correlations of resting-state functional MRI signal and structural connectivity networks from diffusion tensor imaging tractography in 85 USSHL patients (41 for left side and 44 for right side) and 85 healthy controls. Moreover, for each subject, we quantified coupling between functional and structural connectome. The correlation between functional and structural connectome was constrained by the edges with non-zeros structural connectivity. Graph theoretical analysis was employed to compute network properties. The coupling of functional connectivity network–structural connectivity network between USSHL patients and healthy controls was compared by using permutation tests. To investigate the clinical relevance of altered brain network topologies in USSHL, pearson’s correlation analysis was performed between the clinical variables and the topological properties or the strength of functional–structural connectome coupling.Compared with the control groups, both groups of USSHL patients exhibited a significantly increased clustering coefficient, global efficiency, and local efficiency but a significantly decreased characteristic path length in both functional and structural connectivity networks. These findings suggest that the alteration of network organization already exists in USSHL patients within the acute period and that the connectome of USSHL patients is characterized by a shift toward small-worldization. In addition, the primary increased nodal strength (e.g., nodal betweenness, hubs) was observed in limbic and paralimbic systems primarily，as well as in the auditory network brain areas, which may reflect disease-specific pathophysiology in USSHL. Most importantly, the coupling strength of structural–functional connectome was decreased, and exhibited a negative correlation with some USSHL clinical variables in patients, suggesting that the decoupling strength of functional-structural connectivity might be an important characteristic reflecting the mechanisms of USSHL and may be used as a potential biomarker to detect subtle brain abnormalities in USSHL.This is the first study to explore the altered topological organization in USSHL combining functional and structural connectome, which providing a new way to understand the pathophysiological mechanisms of USSHL. We found, using graph theory analysis, that detectable alteration of network organization occurred in USSHL patients within the acute period at the global and regional level. The structural–functional connectome of USSHL patients is characterized by a shift toward small-worldization with a significant increase in the clustering coefficient, the global efficiency and the local efficiency but a significant decrease in the characteristic path length, which may indicate a plastic reorganization procedure of the brain to compensate for the loss hearing in USSHL. Moreover, the degree of coupling between structural and functional connectome was decreased, which may reflect the pathophysiological mechanisms of USSHL. We hope these findings will help to elucidate unilateral USSHL through a new research perspective and provide insight for the potential pathophysiology.