Cisplatin-based chemotherapy has been widely used for treating a variety of solid tumors including breast, lung and ovarian cancers. Although initial therapeutic success is achieved, a number of tumors are found to be intrinsically resistant or gradually develop resistance to cisplatin treatment, which greatly limits its therapeutic potential. Notably, cisplatin belongs to the platinum compound family, which are known as the only heavy metal containing drugs used for chemotherapy. Our proposed research will focus on a growth-related signaling pathway, named the Hippo pathway, in regulating heavy metal-induced stress response, which results in a unique mechanism accounting for the cisplatin-based chemo-resistance.