Recent studies have shown that IκB kinase α (IKKα) plays an important role in human skin cancer and acts as a major regulator for keratinocyte terminal differentiation and proliferation. IKKα deficiency or mutation is associated with human tumor development; thus, overexpression of IKKα could prevent tumor progression. However, findings suggest that IKKα is equally essential for many other epithelial-derived tumors. In the present study, we discussed the role of IKKα as a tumor suppressor in IKKα-mediated epithelial‑derived tumors and its activation pathway, which is different from the traditional NF-κB pathway. The present study provides theoretical basis for understanding the molecular mechanisms involved in IKKα-related tumors.