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Objective: This article plans to investigate Fbxw8 protein expression in esophageal squamous cell carcinoma tissues. And its effect on the proliferation ability of esophageal squamous cancer KYSE70 cells is analyzed. Methods: We can detect Fbxw8 protein expression in esophageal squamous cell carcinoma tissues with IHC and analysis the expression with the sex, age, lymph node metastasis and tumor stage. We alsodetect the proliferation of KYSE70 cells with CCK 8. Result: Most esophageal squamous carcinoma tissues highly expressed Fbxw8 protein, and the expression was positively correlated with lymph node metastasis and tumor staging (P < 0.05). Fbxw8 siRNAs can significantly cut FBXW8 protein expression, while lowering the cell cycle related protein expression of Cyclin A, Cyclin B1, and inhibiting KYSE70 cell proliferation. Conclusion: Fbxw8 protein highly expressed in esophageal squamous carcinoma tissues, and closely related to tumor staging. Targeted inhibition Fbxw8 protein expression could significantly inhibit the proliferation of esophageal squamous carcinoma cells.