The way people make decisions that have direct consequences to the self and others forms the moral foundation of human society. Although humans are at times impacted by social fairness norms and cooperation, economists have supposed that humans generally prioritize maximizing their own self-interest over others’. Recent psychological studies have shown people to be hyperaltruistic in social decisions, such as moral decision-making. Moral decision-making typically involves a trade-off between maintaining personal benefits and preventing harm to others. Previous human brain imaging studies have found similarities in neural activation between moral and economic decision-making under risk situations. Meanwhile, the way that people balance the gains and losses between themselves and others under social risk situations, especially the underlying neural mechanism, remains unclear. Reputational concern is a potentially important factor during human moral decision-making; that is, people are extremely concerned about how others perceive their behavior, which has a significant impact on prosocial behavior and motivation. Thus, this event-realted potential (ERP) study used the dilemma scenario-priming paradigm to explore how both self-relevance and reputational loss risk interact with behavioral and neural responses during moral decision-making. Participants were instructed to accomplish a moral decision-making task under reputational loss risk situations. Specifically, the participants needed to decide whether they were willing to sacrifice their own interests to help a protagonist (friend, acquaintance, or stranger) facing dilemmas of reputational loss risk (low to high risk). In addition to behavioral data and ERP analyses, we conducted spectral analysis to examine the neural oscillations underlying moral decision-making. Behavioral results showed that under low risk of reputational loss conditions, participants demonstrated a differential altruistic tendency, indicating that participants made more helping choices and subsequently reported weaker unpleasant experiences toward friends compared with acquaintances and strangers. Nonetheless, the participants showed an obvious “acquaintance effect”, suggesting that participants took longer time to make decisions and experienced stronger displeasure. Electrophysiological results revealed that moral decision-making toward acquaintances under low reputational loss risk conditions also elicited larger P260-N2-LPP (300–450 ms) effects during emotional and cognitive processing, compared with friends and strangers. Spectral analysis results showed that the delta- (1–4 Hz, 200–300 ms) and alpha-band powers (8–13 Hz, 300–600 ms) for moral decision-making toward acquaintances were significantly larger compared with the case for friends and strangers, under low risk of reputational loss conditions. However, these effects of all indices weakened or disappeared under high risk of reputational loss conditions. The present results suggested that the moral principles that guide interpersonal moral decision-making can best be described as egoistically biased altruism, and that uncertainty in interpersonal relationships brings emotional and cognitive burden to moral decision-making. Moreover, reputational concerns may play a crucial role in limiting selfish tendencies and eliminating uncertainties.