Long non-coding RNAs (lncRNAs) regulate gene expression and carcinogenesis. The lncRNA heart and neural crest derivatives expressed transcript 2 antisense RNA 1 (HAND2‑AS1) suppresses tumor growth, and its expression level was lower in tumor tissues than in adjacent normal tissues of most types of human cancers, including non-small cell lung cancer, ovarian cancer, breast cancer, gastric cancer, colorectal cancer, cervical cancer, endometrial cancer, prostate cancer, and esophagus squamous cell carcinoma. However, one study reported that the HAND2‑AS1 expression was upregulated in hepatocellular carcinoma tissues comparing with non-tumor tissues and it promoted tumor development. The aberrant expression of HAND2-AS1 was strongly linked to tumor progression and prognosis. Moreover, HAND2-AS1 was involved in tumor cell proliferation, differentiation, apoptosis, and cellular glucose metabolism. This review summarizes data on the expression profile, functions, underlying mechanism, and clinical value of HAND2-AS1 in cancer. The expression profile of HAND2-AS1 in 33 tumors was evaluated by bioinformatics analysis of The Cancer Genome Atlas.