Long non-coding RNAs (lncRNAs) are a kind of translational-repressor RNAs composed of more than 200 nucleotides and formerly considered as transcriptional noise. Recently studies have shown that lncRNAs could bind to multiple biomolecules such as DNA, transcription factors, RNA, chromatin complexes and proteins, and regulate target gene expression at multi-levels, thus playing an essential role in human tumors. DLX6-AS1, a recently discovered oncogenic lncRNA, is highly expressed in various human tumors, including lung cancer, liver cancer and pancreatic cancer. This paper mainly reviewed the regulatory mechanism of DLX6-AS1 as a competitive endogenous RNA (ceRNA) in tumor cell proliferation, cell apoptosis, angiogenesis, epithelial-mesenchymal transformation, chemotherapy resistance and metabolic changes. Furthermore, the translational value of DLX6-AS1 in cancer was also elucidated, which suggested its potential as a diagnostic or prognostic biomarker in cancer. In summary, this present article not only makes an in-depth analysis of the expression changes and carcinogenic mechanism of DLX6-AS1 in various human cancers, but also provides a new breakthrough for the diagnosis and treatment of cancers.