Simple Summary As an adaptor protein, PDCD10 is involved in regulation of diverse biological processes by interacting with multiple molecules. Recently, growing amounts of studies have focused on function of PDCD10 in cancers. However, PDCD10 seems to have a dual role (either pro- or anti-tumor effects) in various cancer types, which may depend on cell/tissue specificity with different cellular interactors. In this review, we provided an overview of the structure and molecular functions of PDCD10, and summarized the knowledge of the dual role of PDCD10 in cancers, with a view to future development and application of PDCD10 as a clinical therapeutic target in cancers. Programmed cell death 10 (PDCD10) was initially considered as a protein associated with apoptosis. However, recent studies showed that PDCD10 is actually an adaptor protein. By interacting with multiple molecules, PDCD10 participates in various physiological processes, such as cell survival, migration, cell differentiation, vesicle trafficking, cellular senescence, neurovascular development, and gonadogenesis. Moreover, over the past few decades, accumulating evidence has demonstrated that the aberrant expression or mutation of PDCD10 is extremely common in various pathological processes, especially in cancers. The dysfunction of PDCD10 has been strongly implicated in oncogenesis and tumor progression. However, the updated data seem to indicate that PDCD10 has a dual role (either pro- or anti-tumor effects) in various cancer types, depending on cell/tissue specificity with different cellular interactors. In this review, we aimed to summarize the knowledge of the dual role of PDCD10 in cancers with a special focus on its cellular function and potential molecular mechanism. With these efforts, we hoped to provide new insight into the future development and application of PDCD10 as a clinical therapeutic target in cancers.