Self-criticism is strongly correlated with a range of psychopathologies, such as depression, eating disorders and anxiety. In contrast, self-reassurance is inversely associated with such psychopathologies. Despite the importance of self-judgements and evaluations, little is known about the neurophysiology of these internal processes. The current study therefore used a novel fMRI task to investigate the neuronal correlates of self-criticism and self-reassurance. Participants were presented statements describing two types of scenario, with the instruction to either imagine being self-critical or self-reassuring in that situation. One scenario type focused on a personal setback, mistake or failure, which would elicit negative emotions, whilst the second was of a matched neutral event. Self-criticism was associated with activity in lateral prefrontal cortex (PFC) regions and dorsal anterior cingulate (dAC), therefore linking self-critical thinking to error processing and resolution, and also behavioural inhibition. Self-reassurance was associated with left temporal pole and insula activation, suggesting that efforts to be self-reassuring engage similar regions to expressing compassion and empathy towards others. Additionally, we found a dorsal/ventral PFC divide between an individual's tendency to be self-critical or self-reassuring. Using multiple regression analyses, dorsolateral PFC activity was positively correlated with high levels of self-criticism (assessed via self-report measure), suggesting greater error processing and behavioural inhibition in such individuals. Ventrolateral PFC activity was positively correlated with high self-reassurance. Our findings may have implications for the neural basis of a range of mood disorders that are characterised by a preoccupation with personal mistakes and failures, and a self-critical response to such events.