Ubiquitin (Ub) is a small protein that can be attached to substrate proteins to direct their degradation via the proteasome. Deubiquitinating enzymes (DUBs) reverse this process by removing ubiquitin from its substrate protein. Over the past few decades, ubiquitin-specific protease 14 (USP14), a member of the DUBs, has emerged as an important player in various types of cancers. In this article, we review and summarize biological function of USP14 in tumorigenesis and multiple signaling pathways. To determine its role in cancer, we analyzed USP14 gene expression across a panel of tumors, and discussed that it could serve as a novel bio-marker in several types of cancer. And recent contributions indicated that USP14 has been shown to act as a tumor-promoting gene via the AKT, NF-κB, MAPK pathways etc. Besides, drugs targeting USP14 have shown potential anti-tumor effect and clinical significance. We focus on recent studies that explore the link between USP14 and cancer, and further discuss USP14 as a novel target for cancer therapy.