Abstract Cancer is one of the leading causes of death worldwide with a high risk of incidence and mortality. Long non-coding RNAs (lncRNAs) have been shown to participate in various biological processes, including tumorigenesis and progression. The HOXD-AS1 (also known as HAGLR and Mdgt) gene is located between the HOXD1 and HOXD3 genes in the HOXD cluster and has been reported to play a critical role in the development and progression of cancers. This review summarizes the current knowledge on the biological functions and mechanisms of HOXD-AS1 in different human cancers, including bladder, cervical, colorectal, gastric, ovarian, and prostate cancers, glioma, hepatocellular carcinoma, melanoma, osteosarcoma, and non-small cell lung cancer. The aberrant expression of HOXD-AS1 in these cancers was related with clinical features of patients with cancers. HOXD-AS1 regulates the growth, invasion, and migration of tumor cells through different underlying mechanisms. In conclusion, HOXD-AS1 may be considered as a promising diagnostic/prognostic biomarker or a novel therapeutic target for cancers. Highlights • HOXD-AS1 expression is aberrant in cancers. • HOXD-AS1 is associated with clinical features of patients with cancers. • HOXD-AS1 regulates the growth, invasion, and migration of cancer cells through different underlying mechanisms. [ABSTRACT FROM AUTHOR]