This study investigated 42,643 eighth grade students from 762 secondary schools in 104 districts and counties in the Z province of mainland China and also test the mediating role of self-efficacy in teacher-student relationship prediction of academic achievement. The results show that there are certain gender differences and regional differences in teacher-student relationship, but they have no practical significance; teacher-student relationship and self-efficacy can significantly predict mathematics academic achievement and both have a positive effect; self-efficacy plays an intermediary role between teacher-student relationship and mathematics achievement, and the ratio of the mediating effect to the total effect is 68%.