The B7-H7 is the newest addition to the B7 family of proteins that is present in the majority of malignancies. In this respect, the goal of the work was to investigate the impact of B7-H7 inhibition on breast cancer cells when paclitaxel and small interference RNA (siRNA) were combined. B7-H7 siRNA was used with Paclitaxel to treat MCF-7 cells. The IC50 of Paclitaxel and the cell survival was then assessed through using MTT assay. Investigation was conducted using flow cytometry to both the induction of apoptosis and the cell cycle. In addition, the clonogenic capacity of MCF-7 cells was investigated. Furthermore, qRT-PCR, was used to evaluate expression of genes. Our results demonstrated that suppressing B7-H7 sensitizes MCF-7 cells to Paclitaxel by triggering apoptosis and altering the expression of critical apoptosis mediator genes. In addition, the cell cycle was stopped in the sub-G1 and also G2-M phases as a result of the combination therapy leading prevention of developing colonies by MCF-7 cells. B7-H7 silencing improved the chemosensitivity of MCF-7 cells to Paclitaxel and demonstrated antiproliferative effects. After the adequate study has been conducted, this strategy may be regarded as a possible alternative treatment option for this cancer.