Hepatocellular carcinoma (HCC) is one of the most common types of cancer across the world. Hyaluronic acid (HA) has been reported to serve an important role in tumor extension, progression, migration and invasion. In addition, the receptor for HA-mediated motility (RHAMM) has been demonstrated to be overexpressed in different types of cancer. However, whether the upregulation of RHAMM contributes to hepatocarcinogenesis of HCC remains unclear. The present study examined the RHAMM expression in 187 HCC patients by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). RHAMM expression was significantly upregulated in liver cancer tissues compared with that observed in adjacent normal liver tissues. The IHC analysis demonstrated that RHAMM was overexpressed in 18 (72.0%) of the 25 HCC tissues. Furthermore, overexpression of RHAMM was associated with tumor-node-metastasis (TNM), the presence of vascular invasion and recurrence. Notably, the present study indicated that the overexpression of RHAMM was closely associated with the shorter disease-free and overall survival, so it may be a potential independent predictor for disease-free and overall survival of HCC patients. In conclusion, the upregulation of RHAMM is associated with HCC progression and prognosis; and it may be a potential independent predictor of disease-free and overall survival of HCC following surgical resection.