The ability to deceive others is a high-level social and cognitive function. It has been suggested that response conflict and cognitive control increase during deceptive acts but this hypothesis has not been evaluated directly. Using fMRI, we tested this prediction for the execution of an intentional false response. Subjects were instructed to respond truthfully or falsely to a series of yes/no questions that were also varied in autobiographical and nonautobiographical content to further examine the influence of personal relevance when lying. We observed an interference effect (longer reaction times for false versus true responses) that was accompanied by increased activation within the anterior cingulate, caudate and thalamic nuclei, and dorsolateral prefrontal cortex (DLPFC), a circuit that has been implicated in response conflict and cognitive control. Behavioral and neural effects were more robust when falsifying autobiographical responses relative to nonautobiographical responses. Furthermore, a correlation between reaction time and left caudate activity supported the presence of increased response inhibition when falsifying responses. When presented with self-relevant (autobiographical) stimuli regardless of response condition, the mesial prefrontal and posterior cingulate cortices were recruited. Neural activity within these two regions and the anterior cingulate cortex (ACC) also showed correlations with self-report personality measures from the Psychopathic Personality Inventory (PPI). Overall, we conclude that the process of interference is inherent to the act of falsifying information and that the amount of conflict induced and cognitive control needed to successfully execute false responses is greater when dealing with personal information.