This study investigated the gender differences in deception and their neural basis in the perspective of two‐person neuroscience. Both male and female dyads were asked to perform a face‐to‐face spontaneous sender–receiver deception task, while their neural activities in the prefrontal cortex (PFC) and right temporal parietal junction (rTPJ) were recorded simultaneously using functional near‐infrared spectroscopy (fNIRS)‐based hyperscanning. Male and female dyads displayed similar deception rate, successful deception rate, and eye contact in deception trials. Moreover, eye contact in deception trials was positively correlated with the success rate of deception in both genders. The fNIRS data showed that the interpersonal neural synchronization (INS) in PFC was significantly enhanced only in female dyads when performed the deception task, while INS in rTPJ was increased only in male dyads. Such INS was correlated with the success rate of deception in both dyads. Granger causality analysis showed that no significant directionality between time series of PFC (or rTPJ) in each dyad, which could indicate that sender and receiver played equally important role during deception task. Finally, enhanced INS in PFC in female dyads mediated the contribution of eye contact to the success rate of deception. All findings in this study suggest that differential patterns of INS are recruited when male and female dyads perform the face‐to‐face deception task. To our knowledge, this is the first interbrain evidence for gender difference of successful deception, which could make us a deeper understanding of spontaneous face‐to‐face deception.