Profound sensorineural hearing loss (SNHL) is an auditory disability associated with auditory and cognitive dysfunction. Due to distinct pathogenesis, some associated structural and functional changes within the brain have been investigated in previous studies, but whole-brain structural alterations are incompletely understood. We extended the exploration of neuroanatomic differences in whole-brain structure in children with profound SNHL who are primarily users of Chinese sign language (CSL). We employed surface-based morphometry (SBM) and subcortical analyses. T1-weighted magnetic resonance images of 26 children with profound SNHL and 27 age- and sex-matched children with normal hearing were analyzed. Compared with the normal control (NC) group, children with profound SNHL showed diverse structural changes in surface-based and subcortical analyses, including decreased cortical thickness in the left postcentral gyrus, superior parietal lobule, paracentral lobule, precuneus, the right transverse temporal gyri, and the middle temporal gyrus; a noticeable increase in the Local Gyrification Index (LGI) in the left precuneus and superior parietal lobule; and diverse changes in gray-matter volume (GMV) in different brain regions. Surface-based vertex analyses revealed regional contractions in the right thalamus, putamen, pallidum, and the brainstem of children with profound SNHL when compared with those in the NC group. Volumetric analyses showed decreased volumes of the right thalamus and pallidum in children with profound SNHL. Our data suggest that children with profound SNHL are associated with diffuse cerebral dysfunction to cortical and subcortical nuclei, and revealed neuroplastic reorganization in the precuneus, superior parietal lobule, and temporal gyrus. Our study provides robust evidence for changes in connectivity and structure in the brain associated with hearing loss.