Objective：This study explored the effects of knocking down apolipoprotein E（APOE）on the proliferation，migration， invasion，and other malignant characteristics of prostate cancer cells through in vitro experiments，and validated them through nude mouse in vivo experiments. Methods：The expression levels of APOE in three human prostate cancer cell lines LNCap，DU145，and PC - 3 were downregulated by transfecting small interfering RNA（siRNA）. Cell viability and sensitivity to anticancer drugs were detected through CCK-8 experiments，cell proliferation ability was detected through clone formation assay，cell migration and invasion were detected using transwell assay，the EdU assay was used to detect the proliferation of prostate cancer cells，and the effects of knocking down APOE and using androgen receptor inhibitor on prostate cancer tumor growth were investigated in vivo by nude mouse tumorigenesis experiments. Results：siRNA - induced downregulation of APOE expression significantly reduced the viability， proliferation，migration，and invasion ability of LNCap，DU145，and PC - 3 cells，increased cell sensitivity to anticancer drugs，and reduced the percentage of cells with relative polarization fluorescence. The results of in vivo experiments also showed that knocking down APOE significantly slowed down the growth rate of tumors，and the addition of androgen receptor inhibitor showed a more significant anti-cancer effect. Conclusion：APOE could regulate a series of malignant behaviors such as proliferation and metastasis of prostate cancer cells，and the expression regulation of APOE may play a crucial role in inhibiting the malignancy and progression of prostate cancer.