Objective To investigate the relationship between the expression of prostate-specific membrane antigen (PSMA) and the clinicopathological features and prognosis of hepatocellular carcinoma (HCC).Methods The clinical data of 100 HCC patients admitted to the Haikou Affiliated Hospital of Central South University Xiangya School of Medicine between Jan. 2014 and Dec. 2015 were analyzed retrospectively. The expressions of PSMA and CD31 were detected by immunohistochemistry staining (IHC). According to the expression level of PSMA, the patients were divided into the low PSMA expression group (n=72) and high PSMA expression group (n=28). The relationship of the expression level of PSMA with the clinicopathological features and prognosis was analyzed. Cox proportional risk model was used to analyze the prognostic factors of HCC patients.Results The expression level of PSMA in HCC was related to the differentiation degree, T stage, lymph node metastasis, TNM stage, Ki-67, distant metastasis during follow-up and BCLC stage (P<0.05). Univariate and multivariate Cox regression analysis showed that the highly-expressed PSMA, TNM stage Ⅲ-Ⅳ, Ki-67 ≥10%, and BCLC stage Ⅲ-Ⅳ were independent risk factors for prognosis of HCC patients (P<0.05). The results of Kaplan-Meier survival curve showed that the 5-year survival rate of patients with lowly-expressed PSMA in HCC was significantly higher than that of patients with highly-expressed PSMA (P<0.05).Conclusion The highly-expressed PSMA is not conducive to the prognosis of patients with HCC. PSMA may be a new prognostic index and target of vascular therapy for HCC patients.