PEST-containing nuclear protein (PCNP), a short-lived small nuclear protein with 178 amino acids, is a nuclear protein containing two PEST sequences. PCNP is highly expressed in several malignant tumors such as cervical cancer, rectal cancer, and lung cancer. It is also associated with cell cycle regulation and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Wnt signaling pathways during tumor growth. The present article discuss how PCNP regulates the PI3K/AKT/mTOR and Wnt signaling pathways and related proteins, and the ubiquitination of PCNP regulates tumor cell cycle as well as the progress of the application of PCNP in the pathophysiology and treatment of colon cancer, human ovarian cancer, thyroid cancer, lung adenocarcinoma and oral squamous cell carcinoma. The main relevant articles were retrieved from PubMed, with keywords such as PEST-containing nuclear protein (PCNP), cancer (tumor), and signaling pathways as inclusion/exclusion criteria. Relevant references has been included and cited in the manuscript.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.