Abstract: Objective：To explore the expression of FK506 binding protein 65 (FKBP65) in hepatocellular carcinoma (HCC) tissues and evaluate the prognosis value of FKBP65 in HCC. Methods：The expression of FKBP65 was detected by immunohistochemical staining in 147 HCC tissue samples. The correlation between FKBP65 and other clinical and pathological characteristics was analyzed. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard regression model analysis were performed to investigate the overall survival and recurrence free survival. Results：FKBP65 was expressed both in the tumor cells and stroma cells in the HCC tissues. The FKBP65 expression in stroma cells was positively associated with tumor sizes (P=0.001). The univariate analysis showed that the patients with high FKBP65 expression in stroma cells group had lower overall survival and recurrence free survival compared with low FKBP65 expression group (P=0.002, P=0.011). The Multivariate analysis showed that the high FKBP65 expression in stroma cells was an independent risk factor for the overall survival (HR=2.676, 95%CI 1.463-4.859) and recurrence free survival (HR=1.731, 95%CI 1.032-2.905). Conclusions：High FKBP65 expression in stroma cells of the HCC tissue might be associated with poor clinical outcomes.