〔Abstract〕 Objective To analyze the relationship between E26 transformation-specific(ETS) variant 4(ETV4) expression and clinicopathological parameters of colon cancer, and to explore its effect and molecular mechanism on colon cancer invasiveness. Methods Over expression genes in colon cancer were identified by GEPIA and R2 online bioinformatics analysis.The ETV4 protein level of colon cancer tissues and adjacent normal tissues was detected by immunohistochemistry, and the relationship between ETV4 level and pathological parameters of colon cancer was analyzed.The mRNA expression of ETV4 in colon cancer cell lines and immortal normal colonic epithelial cells.After silencing or overexpression of ETV4 in LOVO cells, the invasiveness was evaluated by Transwell assay.The downstream genes of ETV4 were predicted by bioinformatic analysis, and confirmed by Western blot. Results GEPIA and R2 online bioinformatics analysis showed that ETV4 and MMP7 were highly expressed in colon cancer tissues.Immunohistochemical results showed that ETV4 expression was higher in cancer tissues than in paired paracancer tissues, and its expression level was positively correlated with T,N,and M grades of tumors.RT-qPCR results showed that ETV4 mRNA level in colon cancer cell lines HCT116,LS174 T,SW480,LOVO,SW620,and RKO were significantly higher than that in immortal normal colonic epithelial cells FHC.Transwell assay showed that ETV4 promoted the invasiveness of LOVO cells.R2 online bioinformatic analysis showed that ETV4 was positively correlated with MMP7.Western blot results showed that ETV4 upregulated MMP7 in LOVO.Meanwhile, rescue experiments showed that silencing MMP7 reversed the increased invasiveness of LOVO by ETV4. Conclusion The expression of ETV4 increases in colon cancer tissues and cell lines and promotes the invasiveness of colon cancer cells by upregulation of MMP7.