BACKGROUND AND AIM Fbxw7 is a tumor suppressor gene through ubiquitination and degradation of multiple oncoproteins. Loss of Fbxw7 expression is frequently observed in various human cancers. In the present study, we examined the role of Fbxw7 expression in both non-tumor liver tissues and tumor tissues on clinicopathological significance. METHODS Sixty-six patients with hepatocellular carcinoma (HCC), who underwent hepatectomy, were divided into two groups: high and low gene-expression group, based on the Fbxw7 expression level. We compared the clinicopathological factors between the high expression and low expression groups in both tumor and non-tumor tissues. RESULTS Fbxw7 messenger RNA expression level in the non-tumor tissues was significantly higher than that in the tumor tissues. In the analysis of Fbxw7 expression in tumor and non-tumor tissues, disease-free survival rate in the Fbxw7 high expression group was significantly higher than that in the low expression group. In multivariable analysis, Fbxw7 low expression in both tumor and non-tumor tissue was detected as the strongest independent risk factor for HCC recurrence. CONCLUSIONS Low Fbxw7 expression in both tumor and non-tumor tissue may be an independent prognostic factor for tumor recurrence after hepatectomy in patients with HCC.