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Abstract Objective To evaluate the difference between hepatitis B virus related hepatocellular carcinoma (HBV-HCC) and non-HBV non-HCV hepatocellular carcinoma (NBNC-HCC) patients based on clinical features and prognosis. Methods A total of 175 patients with HCC were enrolled. Patients’ characteristics were extracted from medical records. Among them, 107 patients were positive for HBsAg and negative for HCV-Ab while 68 patients were negative for HBsAg and HCV-Ab. Results The patients in the NBNC-HCC group were significantly older than those in the HBV-HCC group (P = 0.045). Moreover, vascular invasion was found in 23.4% of HBV-HCC patients, which was significantly higher than that in the NBNC-HCC patients with 10.3% (P = 0.029). Kaplan-Meier analysis revealed that HBV-HCC patients had significantly worse outcomes in terms of overall survival (P = 0.036). Compared with the NBNC-HCC patients, the HBV-HCC patients had a significantly worse disease-free survival (P = 0.0018). The multivariate analysis results indicated that TNM stage (HR = 1.541, 95%CI 1.072–2.412, P = 0.002) and HBV infection (HR = 1.087, 95%CI 1.012–1.655, P = 0.042) were independent risk variables for overall survival. While vascular invasion (HR = 1.562, 95%CI 1.013–2.815, P = 0.042) and HBV infection (HR = 1.650, 95%CI 1.017–2.676, P = 0.037) were independent risk factors associated with disease-free survival. Conclusion Our data revealed that HBV-HCC is more common in young males with vascular invasion, while NBNC-HCC occurs mostly in elderly patients, and overall survival rate is significantly better than that of HBV-HCC. Our study therefore provides evidence that patients with HBV-HCC require closer follow-up due to their poor prognosis.