It has been well documented that Machiavellianism has a positive effect on break-up distress. However, there are few research explored the internal mechanism. In this study, we investigated the mediating role of self-concealment and the moderating role of gender. Machiavellianism Personality Scale, Self-Concealment Scale and Break-up Distress Scale was distributed through an online questionnaire platform. A sample of 869 undergraduate students was received, and their age ranged from 16 to 25 years old (M = 19.48, SD = 1.15). As we predicted, the relationship between Machiavellianism and break-up distress was partially mediated by self-concealment. The direct effect of Machiavellianism on break-up distress and the mediating effect of self-concealment were moderated by gender. Specifically, compared with boys, the effect of Machiavellianism on self-concealment was stronger for girls, while the effect of Machiavellianism on break-up distress was stronger for boys. These findings confirm how Machiavellianism affects break-up distress and provide new intervention ideas for solving the psychological crisis of college students after the dissolution of romantic relationships.