Objective To discuss the effect of oridonin on the proliferation， migration， epithelial-mesenchymal transition （EMT）， and apoptosis of the human nasopharyngeal carcinoma HONE-1 cells， and to clarify its related antitumor mechanism. Methods The HONE-1 cells were treated with different concentrations （0， 5， 10， 20， 40， 80， and 160 mg·L^-1） of oridonin for 48 h. CCK-8 method was used to detect the inhibitory rates of proliferation of the cells in various groups and the drug concentration for subsequent experiment was confirmed.The HONE-1 cells were divided into control group， 3 mg·L^-1 oridonin group， and 6 mg·L^-1 oridonin group. After 24 and 48 h of culture， CCK-8 method was used to detect the proliferation activities of the cells in various groups； 5-ethynyl-2'-deoxyuridine （EdU） method was used to detect the rates of EdU-positive cells in various groups； colony formation assay was used to detect the numbers of clone formation in the cells in various groups； Transwell chamber experiment and cell wound assay were used to detect the numbers of migration cells and the scratch healing rates of the cells in various groups； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of cyclin-dependent kinase 1 （CDK1） and cyclin-dependent kinase 4 （CDK4） mRNA in the cells in various groups； Western blotting method was used to detect the expression levels of E-cadherin， Vimentin， Caspase-3， and poly ADP-ribose polymerase 1 （PARP1） proteins in the cells in various groups. Results The CCK-8 method results showed that the half-maximal inhibitory concentration （IC₅₀） of oridonin at 48 h was 12.18 mg·L^-1，and 1/4 IC₅₀ and 1/2 IC₅₀ values were used as the concentrations for subsequent experiments. Compared with control group， after treated for 24 and 48 h， the proliferation activities of the cells in 3 and 6 mg·L^-1 oridonin groups were decreased （P<0.05 or P<0.01）， the rate of EdU-positive cells were decreased （P<0.05 or P<0.01）， the numbers of clone formation and migraton cells were decreased （P<0.05 or P<0.01）， the scratch healing rates were decreased （P<0.05 or P<0.01）， the expression levels of CDK1 and CDK4 mRNA in the cells were decreased （P<0.05 or P<0.01）， the expression levels of E-cadherin， Caspase-3， and PARP1 proteins were increased （P<0.05 or P<0.01）， and the expression levels of Vimentin protein were decreased （P<0.05）. Conclusion Oridonin can inhibit the proliferation， clone formation， and migration of the human nasopharyngeal carcinoma HONE-1 cells by downregulating the expression of cell cycle-related proteins and EMT， and promote the apoptosis to exert an antitumor effect.