We explored the influence of the TCL6/miR-876-5p axis on breast cancer cell proliferation and migration. Using The Cancer Genome Atlas (TCGA) database, we evaluated the expression of TCL6 in breast cancer patients and studied its effects on cell proliferation, migration, and the cell cycle in vitro. The regulatory effect of miR-876-5p on myosin light chain-2 (MYL2) 3' untranslated regions (3'UTR) was analyzed through luciferase reporter assays, and rescue experiments confirmed TCL6-driven upregulation of MYL2 via a competitive RNA binding mechanism. Furthermore, we used a mouse subcutaneous tumor model to assess the impact of TCL6 knockdown combined with immune checkpoint blockade therapy. Our results indicated that higher TCL6 expression correlated with a favorable prognosis in breast cancer patients. In vitro experiments showed that knockdown of TCL6 and MYL2 enhanced breast cancer cell proliferation and migration. The luciferase and rescue assays demonstrated that TCL6 interacted with miR-876-5p to upregulate MYL2, thereby inhibiting cell proliferation and migration. Both in vitro and in vivo studies revealed that overexpression of TCL6 suppressed tumor growth and improved the response to PD-1 immunotherapy in tumor-bearing mice. This research highlights the pivotal role of lncRNA TCL6 in breast cancer development via a ceRNA network involving miR-876-5p and MYL2, suggesting a novel molecular target for breast cancer therapy.