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This study reports on an empirical investigation of the association between teacher-student relationship and mathematics achievement via the mediation effect of motivational beliefs in the Chinese context with 158156 eighth graders. The serial mediation model revealed that with gender controlled, the positive association between teacher-student relationship and mathematics achievement was serially and completely mediated by mathematics interest and self-efficacy. The findings suggest that a supportive teacher-student relationship can help students develop stronger mathematics interest and self-efficacy, which in turn promote their superior gains in mathematics performance. The present results deepen our understanding of the influential mechanism of the teacher-student relationship on students’ mathematics learning processes and hold substantive theoretical and practical implications for educational researchers as well as teachers.