Background <p>Perceived discrimination is a source of social stress that has been widely proven to negatively impact individuals’ mental health, especially among adolescents, potentially leading to emotional problems such as anxiety, depression, and loneliness. The current study constructed a chain mediation model and a moderated mediation model to explore whether perceived discrimination is associated with loneliness among adolescents and to understand the underlying mechanisms.</p> Methods <p>We surveyed 1,732 middle school students (886 were male [51.15%] and 846 were female [48.85%]) from Jiangxi Province, China, using the perceived discrimination scale for adolescents, the UCLA loneliness scale, the school bullying questionnaire, the suicide self-injury ideation questionnaire, and the teacher-student relationship scale.</p> Results <p>The findings indicate that there is a significant association between perceived discrimination and loneliness, with school bullying and suicide self-injury ideation serving as statistical mediators. Additionally, the teacher-student relationship score moderates the impact of perceived discrimination on suicide self-injury ideation, showing that a high-quality teacher-student relationship can mitigate the negative effects of perceived discrimination, thereby reducing loneliness.</p> Conclusion <p>The current study shows that perceived discrimination is an important predictor of loneliness in adolescents. School bullying and suicide self-injury ideation serve as mediators in this relationship, and the teacher-student relationship moderates the pathway between perceived discrimination and suicide self-injury ideation. These findings underscore the importance of fostering positive teacher-student relationships as a protective factor, suggesting that such relationships can help mitigate the adverse mental health effects of perceived discrimination.</p>