Nuclear protein‑1 (NUPR1) is also known as Com‑1 or p8. It is a protein primarily found in the nucleus of various cells, including cancer cells, and it has been found to play an important role in cell stress and stress‑related apoptosis. Over the past two decades, NUPR1 has been firmly indicated to play a role in the development and progression of numerous types of cancer, as well as in a number of other pathological conditions, including pancreatitis, diabetes, neurological and inflammatory conditions. The past decade has witnessed a rapid understanding of the biological and cellular mechanisms through which NUPR1 operates on cells and the identification of new variant of the protein. Most importantly, there have been comprehensive studies on the clinical and pathological aspects of NUPR1 and its variant in multiple malignancies and identification of therapeutic methods by targeting the protein. The present review aimed to summarise the current knowledge relating to NUPR1 in human malignancies and to discuss the associated controversies and potential future prospects of this molecule.