► Discriminating infant facial emotions activated mothers’ right prefrontal cortex. ► Discriminating adult facial emotions did not activate mothers’ prefrontal cortex. ► The right prefrontal cortex activity was differed between mothers and non-mothers. ► The right prefrontal cortex is involved in human maternal behavior. A considerable body of research has focused on neural responses evoked by emotional facial expressions, but little is known about mother-specific brain responses to infant facial emotions. We used near-infrared spectroscopy to investigate prefrontal activity during discriminating facial expressions of happy, angry, sad, fearful, surprised and neutral of unfamiliar infants and unfamiliar adults by 14 mothers and 14 age-matched females who have never been pregnant (non-mothers). Our results revealed that discriminating infant facial emotions increased the relative oxyHb concentration in mothers’ right prefrontal cortex but not in their left prefrontal cortex, compared with each side of the prefrontal cortices of non-mothers. However, there was no difference between mothers and non-mothers in right or left prefrontal cortex activation while viewing adult facial expressions. These results suggest that the right prefrontal cortex is involved in human maternal behavior concerning infant facial emotion discrimination.