Objective:To explore the molecular mechanism of resveratrol(RSV)in the treatment of oral squamous cell carcino-ma(OSCC)based on the combination of transcriptome and proteome.Methods:Oral squamous cell carcinoma HSC-3 cells were cul-tured in vitro and divided into the control group and RSV group.Combined transcriptome and proteome analysis was performed in con-trol group and RSV group to screen key targets and related signaling pathways for intervention in OSCC.The cells were divided into blank control group,RSV 50 μmol/L group,and RSV 100 μmol/L group,mRNA expression levels of core differential genes/proteins,namely neural cadherin(N-cadherin),Vimentin,epithelial cadherin(E-cadherin)and matrix metalloproteinase-9(MMP9)were detec-ted by RT-qPCR and Western blot.Results:After RSV treatment of HSC-3 cells,transcriptome analysis showed that there were 422 dif-ferentially expressed genes in RSV group,of which 276 were up-regulated and 146 were down-regulated.Differentially expressed genes were mainly concentrated in epithelial mesenchymal transformation(EMT)signaling pathway.Proteomic analysis showed that there were 644 differentially expressed proteins in RSV group,of which 342 were up-regulated and 302 were down-regulated.By combining transcriptome-proteome comparisons,117 intersection targets were identified,including E-cadherin,N-cadherin,MMP9 and Vimentin in EMT signaling pathways.The results of RT-qPCR showed that RSV up-regulated the expression of E-cadherin mRNA and down-regula-ted the expression of N-cadherin,Vimentin and MMP9 mRNA,which was consistent with the transcriptomic results.Western blot experi-ment results showed that RSV treatment increased the protein expression level of E-cadherin and decreased the protein expression level of N-cadherin,Vimentin and MMP9,which was positively correlated with RSV concentration and consistent with proteomic results.Con-clusion:RSV inhibits the metastasis of oral squamous cell by regulating the expression of EMT signaling pathway molecules E-cadherin,N-cadherin,MMP9 and Vimentin in HSC-3 cells.