To investigate the role of the prefrontal cortex (PFC) in processing multimodal communicative ostensive signals in infants, we measured cerebral hemodynamic responses by using near-infrared spectroscopy (NIRS) during the social interactive play "peek-a-boo", in which both visual (direct gaze) and auditory (infant-directed speech) stimuli were presented. The infants (mean age, around 7 months) sat on their mother's lap, equipped with an NIRS head cap, and looked at a partner's face during "peek-a-boo". An eye-tracking system simultaneously monitored the infants' visual fixation patterns. The results indicate that, when the partner presented a direct gaze, rather than an averted gaze, toward an infant during social play, the infant fixated on the partner's eye region for a longer duration. Furthermore, hemodynamic activity increased more prominently dorsomedial prefrontal cortex (mPFC) in response to social play with a partner's direct gaze compared to an averted gaze. In contrast, hemodynamic activity increased in the right dorsolateral prefrontal cortex (R-lPFC) regardless of a partner's eye gaze direction. These results indicate that a partner's direct gaze shifts an infant's attention to the partner's eyes for interactive communication, and specifically activates the mPFC. The differences in hemodynamic responses between the mPFC and R-lPFC suggest functional differentiation within the PFC, and a specific role of the mPFC in the perception of face-to-face communication, especially in mutual gaze, which is essential for social interaction.