Background Tinnitus is considered to be triggered by aberrant neural activity in the brain. Sound therapy is regarded as a reasonable management option for tinnitus treatment and has been applied in the clinical setting for decades. Hypothesis We hypothesized that sound therapy, a commonly used tinnitus treatment method, would alter the functional connectivity (FC) of brain regions in tinnitus models. Study Type Longitudinal. Population Resting-state functional MRI data were collected from 27 tinnitus patients before and after 12 weeks of sound therapy. Twenty-seven age- and sex-matched healthy controls were also longitudinally scanned at the 12-week timepoint. Field Strength 3.0T MRI system and echo planar imaging (EPI) sequence, 3D brain volume imaging (BRAVO) sequence. Assessment Functional connectivity strength (FCS), a graph-theoretical-based analytic method, was applied to analyze the FC features in the whole brain. Statistical Tests Student's t-test and chi-square test were used for analyses between two groups. A two-way analysis of covariance (ANCOVA) followed by post-hoc analyses was performed to determine differences of FC. Results The interaction effect between the two groups and two scans on FCS was observed in the bilateral thalami and left anterior cingulate cortex (ACC). The fitted FCS values in the bilateral thalami were significantly higher in tinnitus patients at baseline and decreased to a relatively normal range after sound therapy compared with healthy controls. Conversely, the fitted FCS values in the left ACC were within the normal range, but increased after treatment (1.08 +/- 0.29, P < 0.02); however, there was no change in the control group. Importantly, significant correlations were observed between the FCS changes in the right thalamus (P = 0.028), the FC of the right thalamus-right inferior frontal gyrus (P = 0.015), and symptomatic improvement. Data Conclusion Sound therapy may modulate the brain network by altering the gating function of the thalamus as well as enhancing the tinnitus-canceling system. Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019;50:1731-1741.