Objective: To investigate the pathologic features and clinical outcomes of hepatocellular carcinoma (HCC) with hemorrhagic/necrotic phenotype (HN-HCC). Methods: Sixty-seven patients with HN-HCC that was confirmed by surgical findings and pathological examination were prospectively enrolled, and 37 HCC patients without hemorrhagic/necrotic phenotype (NHN-HCC) treated during the same period served as control. The difference in gross pathology between HN-HCC and NHN-HCC was observed, histopathologic profiles and expressions of the Ki-67, hypoxia-inducible factor-1α (HIF-1α) and cleaved-caspase-3 were examined in multiple regions of the HN-HCC specimens, the expressions of carbonic anhydrase IX (CA-IX) and E-cadherin in the HN-HCC specimens were measured, and the difference in postoperative survival rate between HN-HCC and NHN-HCC patients was compared. Results: HN-HCC and NHN-HCC presented notably different gross appearance. Histopathologic examination and immunohistochemical staining showed that among different intratumoral regions of HN-HCC specimens, there were different degrees of cell differentiation and significantly different expression levels of Ki-67, cleaved-caspase-3 and HIF-1α (all P<0.05). In HN-HCC specimens, the positive expression rate was 86.5% (58/67) for CA-IX and 25.3% (17/67) for E-cadherin, and there was a negative correlation between them (r=–2.601, P<0.05). In HN-HCC patients compared with NHN-HCC patients, both 1-, 3- and 5-year overall survival rate (71.9%, 10.7%, 2.8% vs. 87.5%, 35.6%, 3.6%) and tumor-free survival rate (67.0%, 15.4%, 3.2% vs. 81.2%, 34.3%, 4.0%) were significantly decreased (all P<0.05). Conclusion: Hemorrhagic/necrotic phenotype in HCC suggests that the tumor has strong intratumoral heterogeneity and metastasis potential, and the patients may face a poor prognosis.