High-quality friendships are important sources of social support for adolescents. However, friendships characterized by negative features such as frequent conflicts with friends can be significant interpersonal stressors and are detrimental to adolescents’ mental health and well-being. The present study aimed to examine the associations between friendship conflict and three negative emotional states commonly experienced during adolescence (i.e., depression, anxiety, and stress), test the moderating effect of self-compassion on these associations, and investigate whether the moderating effect differed by gender. A total of 861 Chinese adolescents (45.76% girls; Mage = 15.21, SD = 0.73) completed a suite of questionnaires measuring friendship conflict, self-compassion, depression, anxiety, and stress. Utilizing latent interaction models, we found that friendship conflict was positively associated with depression, anxiety, and stress, respectively, while self-compassion was negatively associated with these negative emotions. More importantly, self-compassion moderated the associations between friendship conflict and the three negative emotions, such that the positive associations between friendship conflict and depression, anxiety, and stress were weaker among adolescents with higher levels of self-compassion. We further conducted multiple group analyses and found that the moderating role of self-compassion was only found for boys, but not for girls. These findings highlighted the protective role of self-compassion in helping adolescents, especially boys, cope with friendship conflict.