Neuroimaging and neurophysiology have revealed that multiple areas in the prefrontal cortex (PFC) are activated in a specific memory task, but severity of impairment after PFC lesions is largely different depending on which activated area is damaged. The critical relationship between lesion sites and impairments has not yet been given a clear mechanistic explanation. Although recent works proposed that a whole-brain network contains hubs that play integrative roles in cortical information processing, this framework relying on an anatomy-based structural network cannot account for the vulnerable locus for a specific task, lesioning of which would bring impairment. Here, we hypothesized that (i) activated PFC areas dynamically form an ordered network centered at a task-specific "functional hub" and (ii) the lesion-effective site corresponds to the "functional hub," but not to a task-invariant "structural hub." To test these hypotheses, we conducted functional magnetic resonance imaging experiments in macaques performing a temporal contextual memory task. We found that the activated areas formed a hierarchical hub-centric network based on task-evoked directed connectivity, differently from the anatomical network reflecting axonal projection patterns. Using a novel simulated-lesion method based on support vector machine, we estimated severity of impairment after lesioning of each area, which accorded well with a known dissociation in contextual memory impairment in macaques (impairment after lesioning in area 9/46d, but not in area 8Ad). The predicted severity of impairment was proportional to the network "hubness" of the virtually lesioned area in the task-evoked directed connectivity network, rather than in the anatomical network known from tracer studies. Our results suggest that PFC areas dynamically and cooperatively shape a functional hub-centric network to reallocate the lesion-effective site depending on the cognitive processes, apart from static anatomical hubs. These findings will be a foundation for precise prediction of behavioral impacts of damage or surgical intervention in human brains.