The present study aims to examine the relationship between the cortical midline structures (CMS), which have been regarded to be associated with selfhood, and moral decision making processes at the neural level. Traditional moral psychological studies have suggested the role of moral self as the moderator of moral cognition, so activity of moral self would present at the neural level. The present study examined the interaction between the CMS and other moral-related regions by conducting psycho-physiological interaction analysis of functional images (...) acquired while 16 subjects were solving moral dilemmas. Furthermore, we performed Granger causality analysis to demonstrate the direction of influences between activities in the regions in moral decision-making. We first demonstrate there are significant positive interactions between two central CMS seed regions—i.e., the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC)—and brain regions associated with moral functioning including the cerebellum, brainstem, midbrain, dorsolateral prefrontal cortex, orbitofrontal cortex and anterior insula (AI); on the other hand, the posterior insula (PI) showed significant negative interaction with the seed regions. Second, several significant Granger causality was found from CMS to insula regions particularly under the moral-personal condition. Furthermore, significant dominant influence from the AI to PI was reported. Moral psychological implications of these findings are discussed. The present study demonstrated the significant interaction and influence between the CMS and morality-related regions while subject were solving moral dilemmas. Given that, activity in the CMS is significantly involved in human moral functioning. (shrink)