The Hippo signaling pathway is considered to be a tissue growth regulator and tumor suppressor pathway that controls cell proliferation, differentiation, survival, regeneration and tissue homeostasis. Defects in Hippo kinases and hyperactivation of transcriptional co‑activator with PDZ‑binding motif and Yes‑associated protein (YAP) may contribute to the development of different types of cancer. The Hippo pathway is regulated in a variety of way, of which ubiquitination is of considerable importance. Ubiquitination is a crucial post‑translational protein modification in cancer cells and is an applicable target for pharmacological intervention. Ubiquitin modifications are involved in regulating various physiological processes and are counteracted by deubiquitination. Imbalanced ubiquitination‑deubiquitination is closely associated with tumor initiation and progression. Therefore, the examination of the specific association between the Hippo pathway and ubiquitination is of interest. The present study reviews the modulatory mechanism of ubiquitination‑deubiquitination in the Hippo signaling pathway, the recent progress in identifying therapeutic targets and strategies, and the future directions in the field that may contribute to better tumor diagnosis and treatment.