Cancer is the second leading cause of death in the world. Although significant progress has been made in the treatment of cancer in recent years, the incidence and mortality rate are still high. Therefore, finding effective drugs to treat cancer is still the focus of research. As a natural compound extract, Isoliquiritigenin (ISL) has been widely studied in its anti-tumor effects in recent years. This article reviewed the recent progress of ISL in its anti-cancer, and discusses the role of ISL in suppressing the occurrence of cancer by controlling cell cycle, metastasis, angiogenesis, cell death and immune system. Among them, ISL suppresses the development of cancer through Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin (PI3K/Akt/mTOR), Epidermal Growth Factor Receptor/Extracellular signal-Regulated Kinase 1/2 (EGFR/ERK1/2), Signal Transducer and Activator of Transcript3 (Signal Transducer and Activator of Transcript3). In addition, the roles of ISL in combination with first-line anticancer drugs and its nano-preparations in anti-tumor was also discussed.