〔Abstract〕 Objective To investigate the expression of E3 ubiquitin ligase F-box and WD-40 domain protein 7(FBXW7) in esophageal squamous cell carcinoma(ESCC) and its effect on its biological behavior. Methods The expression of E3 ubiquitin ligase FBXW7 in 171 cases of ESCC and 53 cases of paracancer tissues was detected by immunohistochemistry. The relationship between FBXW7 expression and survival prognosis and clinicopathological features of patients with ESCC was explored. The ESCC cells of the overexpressed FBXW7 group and the ESCC cells of the control group were constructed, and the effects of FBXW7 on the proliferation, migration and invasion of ESCC cells were detected by CCK-8 assay, plate clone formation assay, Transwell cell migration and invasion assay and cell scratches assay. Results The expression of FBXW7 in paracancer tissues was higher than that in ESCC tissues(P=0.002). ESCC with low FBXW7 expression had lower differentiation degree(P=0.011) and TNM stage was earlier in ESCC patients with high FBXW7 expression(P=0.032), and the survival time of patients with high FBXW7 expression was longer than that of patients with low FBXW7 expression(P=0.030). CCK-8 assay results showed that the absorbance of cells in overexpressed FBXW7 group was lower than that in control group(P<0.001), and plate clone formation assay showed that the colony number of overexpressed FBXW7 group was lower than that of the control group(P<0.001). Cell scratches assay results showed that the cell migration rate of the overexpressed FBXW7 group was lower than that of the control group(P<0.001), Transwell cell migration and invasion assay showed that the number of cell migration and invasion in the overexpressed FBXW7 group was lower than that in the control group(P<0.001). Conclusion The expression of FBXW7 is low in ESCC and low expression of FBXW7 suggests poor prognosis. Overexpression of FBXW7 can inhibit the proliferation, migration and invasion of ESCC cells.