In summary, our study is the first to show that TGFBI inhibits cell proliferation and transformation by delaying G1-S phase transition and inducing cellular senescence in mesothelioma and breast cancer cells, indicating that TGFBI may serve as a negative regulatory effector and potential tumor suppressor in the development of malignances such as mesothelioma and breast cancer. Here, TGFBI is linked to mesothelioma.