Objective To investigate the effect of scutellarin(STR)on the proliferation and migration of human prostate cancer cell line(PC-3)and its underlying mechanism.Methods PC-3 cells were divided into low-dose STR group,medium-dose STR group,high-dose STR group,colivelin(STAT3 activator)group,high-dose STR+colivelin group and control group.CCK-8 assay and colony formation experiments were applied to detect cell prolif-eration;Scratch experiment was applied to detect cell migration;Transmission electron microscopy was applied to observe the mitochondrial ultrastructure of PC-3 cells.The intracellular free Fe2+,malondialdehyde(MDA)content and reactive oxygen species(ROS)levels were detected by colorimetric method;RT-qPCR was applied to detect the mRNA expression of member 11 of solute vector family(SLC7A11),proliferating cell nuclear antigen(PCNA)and matrix metalloproteinase-9(MMP-9)in cells;Western blot was used to detected p-STAT3 and GPX4 proteins in cells.Results Compared to control group,the mitochondrial structure of PC-3 cells in the low-dose STR group,medium-dose STR group and high-dose STR group was significantly disrupted.The A450 value,colony formation rate,scratch healing rate,PCNA,SLC7A11,MMP-9 mRNA expression,and p-STAT3,GPX4 protein all reduced.While Fe2+,MDA content,and that ROS level increased with dose-dependent way(P＜0.05).Compared with control group,the destruction of mitochondrial structure in cells from colivelin group improved;The A450 value,colony formation rate,scratch healing rate,PCNA,SLC7A11,MMP-9 mRNA expression and p-STAT3,GPX4 protein all increased,while Fe2+MDA content,and ROS level decreased(P＜0.05).Compared with high-dose STR group,the damage of mitochondrial structure in PC-3 cells in the high-dose STR+colivelin group was re-duced.The A450 value,colony formation rate,scratch healing rate,PCNA,SLC7A11,MMP-9 mRNA expression,and p-STAT3,GPX4 protein increased,while Fe2+,MDA content and ROS level decreased(P＜0.05).Conclusions The mechanism by of STR reducing proliferation and migration of prostate cancer cells is potentially related to the inhibition of STAT3/GPX4 pathway.