Mammalian sterile 20 like kinase (Mst) 1 and Mst2 are stress-activated kinases, activated by various stress stimuli including oxidative stress. Mst1/2 act as tumor suppressor proteins and their deregulation is associated with the development of cancers, such as liver cancer and prostate cancer. Cellular oxidative stress is known to upregulate Mst1/2activity; activation of Mst1/2 induces apoptosis in oxidative stress conditions.Until recently, the exact mechanism/s of Mst1/2 activation and Mst1/2-induced apoptosis under oxidative stress conditions was not clear. But some recent reports have begun to elucidate the mechanisms of Mst1/2 activation by oxidative stress. Not only Mst1/2 activity is regulated by oxidative stress, but Mst1/2 are also involved in the regulation of redox levels in cells. In this short report we will discuss various mechanisms of Mst1/2 activation and Mst1/2-dependent apoptosis in response to oxidative stress.