This review concerns nc886, a 101-nucleotide non-coding RNA (ncRNA). Because nc886 is transcribed by RNA polymerase III (Pol III) and contains a CpG island in its promoter region, its expression is regulated by several transcription factors and the DNA methylation status. These features drive nc886 expression in two opposing directions during tumorigenesis. The known function of nc886 is to bind to and modulate the activity of target proteins such as PKR, Dicer, and OAS1. By being differentially expressed during tumorigenesis and interacting with these proteins, nc886 plays a role in tumor surveillance, promotes or suppresses tumorigenesis, and influences the efficacy of cancer therapy. The multiple roles of nc886 have been well-documented in the literature. In this review, we have summarized this literature and critically discussed the roles and mechanisms of action of nc886 in various cancers.