Cancer, a complex disease which involves abnormalities of multiple cellular pathways, is one of the most serious threatens to human health across the world. Chemotherapy with a single agent or a combined regimen is a standardized strategy for the treatment of almost all human cancers, and the cure rate of cancer increases with the continuous discovery of anticancer agents and the optimization of chemotherapy options. However, drug resistance, especially multidrug resistance, remains an obstacle in the effective treatment of cancer. Hence, it is urgent to develop novel agents with potential activity against cancers, especially drug-resistant forms. Acridine, which bears three fused rings, could intercalate into DNA and interfere with metabolic processes. Recently, acridines have been found with anticancer activity in a variety of malignancies through suppressing cell proliferation, stimulating apoptosis, and inducing cell cycle arrest, retarding migration, invasion and metastasis. Thus, acridines are useful scaffolds for the discovery of novel drug candidates with potent anticancer activity. This review focused on the current scenario of acridine hybrids with potential activity against cancers reported from Jan, 2015 to Feb, 2021. The mechanisms of action, the criteria of compound design as well as structure-activity relationships were also summarized to pave the way for a further rational design of novel anticancer agents.