We also demonstrated that TP53 mutation, DNA hypomethylation, and the expression changes of upstream TFs of CEMIP were likely to cause hyper-expression of CEMIP, and we further identified three potential upstream TFs in BC, namely, EZH2, EGR1, and JUN. Moreover, our findings suggested that CEMIP was closely related to TME and might exert its oncogenic roles by participating in the extracellular matrix formation, mainly increasing CAF, M2 macrophage, and neutrophil infiltration and decreasing CD8+ T cell infiltration. The gene discussed is CEMIP; the disease is breast cancer.