Urotensin II and the associated urotensin II receptor (UTR) are important in the carcinogenesis of hepatocellular carcinoma (HCC). However, the clinical significance of UTR remains to be elucidated. The aim of the present study was to investigate if UTR exhibits the potential to act as a biomarker to predict the prognosis of HCC patients. The effects of UTR on motility and invasion of HCC cells were additionally investigated. UTR expression levels were determined by immunohistochemistry, in 83 HCC patients that previously underwent curative liver resection. The association between UTR levels and clinicopathological data were analyzed. In vitro, the expressions of UTR in QSG-7701, BEL-7402 and MHCC-97H cell lines were determined via western blotting. Small interfering (si)RNA was used to downregulate UTR in BEL-7402 and MHCC-97H cell lines, and the effects of UTR on tumor cell motility were tested by Transwell assay. UTR expression was associated with tumor number, size, histology and tumor node metastasis/Barcelona Clinic Liver Cancer HCC stage. UTR expression levels were additionally associated with recurrence-free and overall survival in HCC patients by Kaplan-Meier curve analysis (P < 0.0001). In vitro, UTR expression levels were increased in BEL-7402 and MHCC-97H cell lines, compared with QSG-7701 (P < 0.05). siRNA-mediated silencing of the UTR gene significantly inhibited cell motility in BEL-7402 and MHCC-97H cells. The results indicated that UTR may be regarded as a novel biomarker to predict outcomes following radical liver resection and as a potential therapeutic target to inhibit invasion and metastasis of HCC.