〔Abstract〕 Objective To investigate the killing effect of Zinc oxide nanoparticles(ZnO NPs) on kidney cancer Caki-1 cells and its correlation with autophagy. Methods Monolayer Caki-1 cells(2×103/well) were prepared in 96-well plates, treated with different concentrations(1、5、10、15、20、25 μg/ml) of ZnO NPs or treated with 15 μg/ml ZnO NPs for different time(6、12、24 h). Thiazole Blue(MTT) assay detected the inhibitory effect of ZnO NPs on Caki-1 cells. Subsequently, Western blot was used to detect the changes of autophagy effect of cells in different treatment groups. Finally, MTT method and Hoechst33342/PI staining method were used to determine the changes of cell viability after ZnO NPs were co-treated with autophagy inhibitors or enhancer. Results ZnO NPs had a dose and time dependent killing effect on Caki-1 cells. ZnO NPs also could elicit dose and time dependent autophagy effect. After the co-treatment of ZnO NPs and Wortmannin, the accumulation of LC3-Ⅱ decreased. The accumulation of LC3-Ⅱ increased after the co-treatment of ZnO NPs with Trehalose, an autophagy inducer. Meanwhile, after the co-treatment of ZnO NPs with the autophagy inhibitor wortmannin or chloroquine, cell viability was higher than that of ZnO NPs treated alone.However, when the cells were treated with ZnO NPs and Trehalose, the cell viability was further reduced. Conclusion ZnO NPs has a dose and time dependent cytotoxic effect on Caki-1 cells, and ZnO NPs can elicit pro-death autophagy effects in Caki-1 cells. Inhibition of autophagy can reduce cell death, and enhancement of autophagy can increase cell death. ZnO NPs can promote the formation of autophagosomes instead of inhibiting the degradation of autophagic substrates.