Cancer is a major problem in public health and is one of the leading causes of mortality worldwide. Many types of cancer cells exhibit aberrant cellular signal transduction in response to stress, which often leads to oncogenesis. Mitogen-activated protein kinase (MAPK) signal cascades are one of the important intracellular stress signaling pathways closely related to cancer. The key molecules in MAPK signal cascades that respond to various types of stressors are apoptosis signal-regulating kinase (ASK) family members; ASK1, ASK2 and ASK3. ASK family members are activated by a wide variety of stressors, and they regulate various cellular responses, such as cell proliferation, inflammation and apoptosis. In this review, we will discuss both the oncogenic and anti-oncogenic roles of the ASK family members in various contexts of cancer development with deeper insights into the involvement of ASK family members in cancer pathology.