Objective:To investigate the role of hyaluronic acid-mediated motion receptor(HMMR)in the malignant progression of esophageal squamous cell carcinoma(ESCC)cells and its potential molecular mechanisms.Methods:8 samples of ESCC tissues and adjacent paracancerous tissues surgically removed at the Fourth Hospital of Hebei Medical University between January 2018 and December 2020,as well as ESCC cells KYSE-30 and KYSE-150,were collected.Western blotting(WB)and immunohistochemistry(IHC)were used to detect the expression of HMMR in ESCC tissues.RNA interference was used to knock down HMMR expression in KYSE-30 and KYSE-150 cells,and qPCR and WB were used to detect the knockdown effect.The effects of HMMR knockdown on the proliferation and invasion abilities of ESCC cells were detected by CCK-8 assay and Transwell assay,respectively.4-nitroquinoline 1-oxide(4NQO)was used to induce carcinogenesis in mice and establish an ESCC model.H-E staining was used to observe the morphological changes of esophagus,and IHC was used to analyze the expressions of HMMR,FAM83D(family with sequence similarity 83 member D),E-cadherin and N-cadherin in tissues of different degrees of carcinogenesis in mice.Results:The expression level of HMMR in human ESCC tissues was significantly higher than that in adjacent paracancerous tissues(all P<0.05).After HMMR knockdown,the proliferation and invasion abilities of KYSE-30 and KYSE-150 cells were significantly reduced(P<0.05 or P<0.01),and the expression level of FAM83D also decreased(all P<0.01).In nude mouse tumor experiment,the body weight of mice in the 4NQO group was lower than that of the control group(all P<0.05).The results of IHC staining showed that HMMR was highly expressed in tumor tissues(P<0.05),and the expression of HMMR in high-grade intraepithelial neoplasia(HGIN)tissues was significantly higher than that in low-grade intraepithelial neoplasia(LGIN)tissues(P<0.001).HMMR was positively correlated with the expressions of FAM83D and N-cadherin(r=0.724,0.870,all P<0.001),and negatively correlated with the expression of E-cadherin(r=-0.714,P<0.001).Conclusion:HMMR is highly expressed in ESCC tissues and may promote the progression of ESCC by up-regulating FAM83D expression.