<p>The prohibitin (PHB) family, including PHB1 and its homolog PHB2, is ubiquitously located in different cellular compartments and plays roles in fundamental cellular processes such as proliferation, differentiation, and apoptosis. Accumulating evidence has indicated that this family contributes to the development of numerous diseases in particular cancers. Aberrant expressions of PHBs can been observed in diverse types of human cancer. Depending on their cell compartment-specific attributes and interacting proteins, PHBs are tightly linked to almost all aspects of cancer biology and have distinct bidirectional functions of tumor-suppression or tumor-promotion. However, the roles of PHBs in cancer have yet to be fully characterized and understood. This review provides an updated overview of the pleiotropic effects of PHBs and emphasizes their characteristic roles in each cancer respectively, with the great expectation to identify potential targets for therapeutic approaches and promising molecular biomarkers for cancer diagnosis and prognostic monitor.</p>