The hub-and-spoke theory of semantic representation fractionates the neural underpinning of semantic knowledge into two essential components: the sensorimotor modality-specific regions and a crucially important semantic hub region. Our previous study in patients with semantic dementia has found that the hub region is located in the left fusiform gyrus. However, because this region is located within the brain damage in patients with semantic dementia, it is not clear whether the semantic deficit is caused by structural damage to the hub region itself or by its disconnection from other brain regions. Stroke patients do not have any damage to the left fusiform gyrus, but exhibit amodal and modality-specific deficits in semantic processing. Therefore, in this study, we validated the semantic hub region from a brain network perspective in 79 stroke patients and explored the white matter connections associated with it. First, we collected data of diffusion-weighted imaging and behavioural performance on general semantic tasks and modality-specific semantic tasks (assessing object knowledge on form, colour, motion, sound, manipulation and function). We then used correlation and regression analyses to examine the association between the nodal degree values of brain regions in the whole-brain structural network and general semantic performance in the stroke patients. The results revealed that the connectivity of the left fusiform gyrus significantly predicted general semantic performance, indicating that this region is the semantic hub. To identify the semantic-relevant connections of the semantic hub, we then correlated the white matter integrity values of each tract connected to the left fusiform gyrus separately with performance on general and modality-specific semantic processing. We found that the hub region accomplished general semantic processing through white matter connections with the left superior temporal pole, middle temporal gyrus, inferior temporal gyrus and hippocampus. The connectivity between the hub region and the left hippocampus, superior temporal pole, middle temporal gyrus, inferior temporal gyrus and parahippocampal gyrus was differentially involved in object form, colour, motion, sound, manipulation and function processing. After statistically removing the effects of potential confounding variables (i.e. whole-brain lesion volume, lesion volume of regions of interest and performance on non-semantic control tasks), the observed effects remained significant. Together, our findings support the role of the left fusiform gyrus as a semantic hub region in stroke patients and reveal its crucial connectivity in the network. This study provides new insights and evidence for the neuroanatomical organization of semantic memory in the human brain.