Objective:To explore the toxicity and dose-response relationship of 4-nm gold nanoparticles (AuNPs) on human lung adenocarcinoma cell line A549. Methods:Sodium citrate solution (the control group) and three concentrations (12.5,25.0 and 50.0 -滋g/ml) of 4-nm AuNPs solution were respectively added to the culture medium of A549 cells for 48 h incubation. The morphology and internalization of AuNPs in A549 cells were observed by transmission electron microscopy (TEM);cell viability of A549 was detected using cell proliferation and toxicity kit;cell cycle and apoptosis of A549 were analyzed by flow cytometry. Results:TEM showed that the shape and size of AuNPs particles were homogeneous and mainly distributed in small vesicles,cytoplasm,lysosomes or the perinuclear region in A549 cells. Compared to the control group,4-nm AuNPs significantly reduced the cell viability in a dose-response relationship (P < 0.05). The results of flow cytometry showed that AuNPs with higher concentration (25 and 50 -滋g/ml) significantly increased the apoptosis of A549 cells (P < 0.05),while no significant difference in cell cycle. Conclusion:AuNPs with size of 4 nm can significantly reduce cell viability and promote apoptosis in a dose-response relationship in A549,which provides a new strategy for the treatment of lung cancer.