Abstract: To analyze the expression features of the hypoxia-inducible factor-1α ( HIF-1α ) in hepatocellular carcinoma ( HCC ) tissues and the effects of HIF-1α silencing on HepG2 cells. Methods: HIF-1α expression was analyzed in the self-control HCC specimens via immunohistochemistry. At 72 h after transfection with the HIF-1α miRNA plasmid, the levels of HIF-1α mRNA and protein  in the HepG2 cells were determined using real-time polymerase chain reaction ( PCR ) and Western blot analysis. The vascular endothelial growth factor (VEGF) and angiopoietin-2 ( ANG-2 ) expressions in the supernate were determined using ELISA. Moreover, the alterations in the cell cycles and apoptosis in the HepG2 cells with miRNA and doxorubicin were measured using a flow cytometer. Results: The positive HIF-1α was brown and granular in the cytoplasm or nucleus. A significant difference was found between HCC ( 80% ) and its surrounding tissues ( 100%, χ2 = 22.35, P < 0.001 ). The features of HIF-1α were correlated with tumor size. At 72 h after transfection, the expressions of HIF-1α mRNA and protein  in HepG2 were down-regulated by 87% and 56%, respectively. VEGF and ANG-2 were also reduced by 54% and 34%, respectively. After a combined doxorubicin and HIF-1α silencing, the apoptotic ratio increased from 22.46% ± 0.61% to 36.99% ± 0.88%. The proportions of the G1 and S phases were up-regulated to 65.68% ± 0.91% and 19.47% ± 1.34%, respectively. Conclusion: The abnormal expression of HIF-1α is associated with the occurrence and development of HCC. In addition, HIF-1α silencing can effectively inhibit HepG2 proliferation.