Purpose The thalamus plays a crucial role in sensorimotor, cognitive and attentional circuit functions. Disruptions in thalamic connectivity are believed to underlie the symptoms of multiple sclerosis (MS). Therefore, assessing thalamocortical structural connectivity (SC) and functional connectivity (FC) may provide new insights into the mechanism of intrinsic functional plasticity in a large-scale neural network. Methods Seventy-eight patients with clinically definite MS at the First Affiliated Hospital of Nanchang University participated in this study from May 2010 to June 2015. After excluding patients who had excessive head motion during scanning (see the Resting-state functional MRI (rs-fMRI) data preprocessing section) and those who did not meet the selection criteria, 20 RRMS patients (18 patients receiving β-interferons; 2 receiving Glatiramer acetate) and well matched HC subjects were included in this study. We used resting-state FC measurement and diffusion tensor imaging probabilistic tractography to study the functional and structural integrity of the thalamocortical system in patients with relapsing-remitting MS (RRMS) and matched healthy controls. Results Voxel-based FC analysis was then used to measure regional neuroplasticity in the thalamic ECRs. Compared with the HC group, the RRMS group showed significantly increased FC between the thalamus and the primary motor cortex (bilateral M1/paracentral lobule), the occipital cortex (right lingual gyrus), the PFC (left middle (orbital) frontal gyrus), and the temporal cortex (right temporal pole) (AlphaSim-corrected P < 0.01); the RRMS group also showed significantly decreased FC between the thalamus and the PFC (left middle frontal gyrus and bilateral superior (medial) frontal gyrus) (AlphaSim-corrected P < 0.01). In the RRMS patients, a reduced track count of the thalamocortical temporal WM tract (3.878×105 vs. 4.623×105), and a smaller volume of the thalamocortical occipital WM tracts (2.651×103 mm3 vs. 3.555×103 mm3) were detected compared with the HC subjects. SC integrity were assessed by measuring the standard DTI parameters of the above-threshold reconstructed tracts. Compared with the HC subjects, in the RRMS patients, decreased FA values were detected in the thalamocortical motor, somatosensory, and prefrontal WM tracts, and increased diffusivity values for MD, AD and RD were detected in all seven thalamocortical tracts (P < 0.05), excluding the AD values of the thalamocortical motor, somatosensory, and premotor tract. In the thalamocortical connections of RRMS patients, we found lesion load-related regional FC in the right temporal pole, which reflected compensatory hyperconnectivity related to lesion-related demyelination. We also found significant correlations between increased diffusivity and slowed cognitive processing (PASAT) or the impact of fatigue (MFIS-5), as well as between connective fiber loss and disease duration. Conclusions In conclusion, compared with HC subjects, minimally disabled RRMS patients exhibited structural disconnections and regional intrinsic functional hyperconnectivity in thalamocortical system. The evidence from SC and FC analyses of the thalamocortical tract suggests a dissociated SC-FC pattern and limited regional functional plasticity to compensate for chronic demyelination-related long-distance structural disconnectivity in minimally disabled RRMS patients.