Previous studies on the brain–brain interaction of deception have shown different patterns of interpersonal brain synchronization (IBS) between different genders. However, the brain–brain mechanisms in the cross-sex composition need to be better understood. Furthermore, there needs to be more discussion about how relationships (e.g., romantic couples vs. strangers) affect the brain–brain mechanism under interactive deception. To elaborate on these issues, we used the functional near-infrared spectroscopy (fNIRS)-based hyperscanning approach to simultaneously measure interpersonal brain synchronization (IBS) in romantic couples (heterosexual) and cross-sex stranger dyads during the sender–receiver game. The behavioral results found that the deception rate of males was lower than that of females, and romantic couples were deceived less than strangers. Significantly increased IBS was observed in the frontopolar cortex (FPC) and right temporoparietal junction (rTPJ) of the romantic couple group. Moreover, the IBS is negatively correlated with the deception rate. No significantly increased IBS was observed in cross-sex stranger dyads. The result corroborated the lower deception of males and romantic couples in cross-sex interactions. Furthermore, IBS in the PFC and rTPJ was the underlying dual-brain neural basis for supporting honesty in romantic couples.