Abstract: Flonicamid is a selective insecticide, mainly registered to control sap-sucking insect pests. However, the mode of action for this insecticide is undefined for years. Recently, the molecular target of flonicamid was disclosed. The previous researches demonstrated that flonicamid caused the mortality of sap-sucking insects by inhibiting the feeding behavior of hemipteran pests. A recent study reported that the molecular target of flonicanmid was inward-rectifying potassium channels (Kir). Flonicamid in nanomole concentration inhibited the Kir channel of rice brown planthopper (Nilaparvata lugens) and disturbed the K⁺ homeostasis and the equilibrium potential across cell membrane, which then disrupted the physiological functions of salivary gland and Malpighian tubules, and finally lead to lethality of insect pests. In this review, the structure and physiological function of Kir channels in insects are summarized, and the mechanism for the mode of action of flonicamid by inhibiting the Kir channels is discussed. Finally, the research progress in high throughtput screening for novel small moleculars targeting at Kir channels of insects with thallium fluorescent probe is introduced, which will highlight the way to discover new insecticidal targets and to create the novel compounds with insecticidal activities.