The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma(HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were hereperformed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Mostof the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, withFn14High accounting for 54.6% (142/260) of all patients. The Pearson χ2 test indicated that Fn14 expression wasclosely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate andmultivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type,Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence(HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this moleculemay be a candidate biomarker for prognosis as well as a target for therapy.