Prolonged auditory sensory deprivation leads to brain reorganization. This is indicated by functional enhancement in remaining sensory systems and known as cross-modal plasticity. In this study we investigated differences in functional brain network topology between deaf and hearing individuals. We also studied altered functional network responses between deaf and hearing individuals with a recording paradigm containing an eyes-closed and eyes-open condition.Electroencephalography activity was recorded in a group of sign language-trained deaf (N = 71) and hearing people (N = 122) living in rural Africa. Functional brain networks were constructed from the functional connectivity between fourteen electrodes distributed over the scalp. Functional connectivity was quantified with the phase lag index based on bandpass filtered epochs of brain signal. We studied the functional connectivity between the auditory, somatosensory and visual cortex and performed whole-brain minimum spanning tree analysis to capture network backbone characteristics.Functional connectivity between different regions involved in sensory information processing tended to be stronger in deaf people during the eyes-closed condition in both the alpha and beta frequency band. Furthermore, we found differences in functional backbone topology between deaf and hearing individuals. The backbone topology altered during transition from the eyes-closed to eyes-open condition irrespective of deafness, but was more pronounced in deaf individuals. The transition of backbone strength was different between individuals with congenital, pre-lingual or post-lingual deafness. Functional backbone characteristics correlated with the experience of sign language. Overall, our study revealed more insights in functional network reorganization caused by auditory deprivation and cross-modal plasticity. It further supports the idea of a brain plasticity potential in deaf and hearing people. The association between network organization and acquired sign language experience reflects the ability of ongoing brain adaptation in people with hearing disabilities.