Abstract： Objective To investigate the effect of extracellular histone on epithelial mesenchy-mal transformation(EMT)and invasion of bladder cancer cells by regulating toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)pathway.Methods T24 bladder cancer cells were cultured and divided into 7 groups:control group,histone H3 groups with different concentrations(50,100,200 μg/mL),solvent control(0.1%DMSO)group,histone H3(200 μg/mL)+sol-vent control(0.1%DMSO)group,and histone H3(200 μg/mL)+NF-κB inhibitor Bay11-7082(10 μmol/L)group.The number of invasion cells and the protein expression levels of E-cad-herin,N-cadherin,Vimentin,TLR4 and phosphorylated P65 NF-κB(p-P65 NF-κB)were de-tected 24 h after administration.Results The number of invasion cells and the expression levels of N-cadherin,Vimentin,TLR4 and p-P65 NF-κB in the histone H3 groups were higher than those in the control group,and the protein expression level of E-cadherin was lower than that in the control group(P<0.05),the number of invasion cells and the expression levels of those proteins were changed with the concentration of histone H3 treatment in a dose-dependent manner.The number of cell invasion and the protein expression levels of N-cadherin,Vimentin and p-P65 NF-κB in the histone H3+Bay11-7082 group were lower than those in the histone H3+solvent control group,and the expression level of E-cadherin was higher than that in the histone H3+solvent control group(P<0.05).Conclusion Extracellular histone promotes EMT and invasion of bladder cancer cells,which is related to the activation of TLR4/NF-κB pathway.