Polo-like kinases (PLKs) play important roles in regulating multiple aspects of cell cycle and cell proliferation. In many cancer types, PLK family members are often dysregulated, which can lead to uncontrolled cell proliferation and aberrant cell division and has been shown to associate with poor prognosis of cancers. The key roles of PLK kinases in cancers lead to an enhanced interest in them as promising targets for anticancer drug development. In consideration of PLK inhibitors and some other anticancer agents, such as BRD4, EEF2K and Aurora inhibitors, exert synergy effects in cancer cells, dual-targeting of PLK and other cancer-related targets is regarded as an rational and potent strategy to enhance the effectiveness of single-targeting therapy for cancer treatment. This review introduces the PLK family members at first and then focuses on the recent advances of single-target PLK inhibitors and summarizes the corresponding SARs of them. Moreover, we discuss the synergisms between PLK and other anti-tumor targets, and sum up the current dual-target agents based on them. Display omitted •Dual-target inhibitors based on PLK, such as PLK1/BRD4 dual inhibitors, and single-target agents were summarized.•We made an insight into the structure-activity relationships of these agents.•We summarize the synergistic mechanisms and effects of PLK based dual-target inhibitors.