Abstract: Objective:To study the expression of hypoxia inducible factor- 1 α (HIF-1 α) in human hepatocel -lular carcinoma (HCC) cells under hypoxia and to explore the effect of silencing HIF-1 α on radiosensi tization in HCC. Methods:The expression of HIF 1 α at di fferent hypoxic cul ture phases was detected by Western blot. HIF1 α speci fic RNAi lentiviral vector was constructed. HIF-1 α si lencing cel ls were screened by blasticidin. RT-PCR and Western blot analysis were used to detect the expressions of HIF-1 α mRNA and protein, respec-tively. Clonogenic assay was employed to observe its effects on the radiosensitivity after HIF- 1 α si lencing. Results: Under hypoxia, the HIF- 1 α protein expression was increased. Transduction of HCC cel ls wi th HIF-1 α RNAi vector resulted in sequence specific silencing with decrease of HIF-1 α expression by 90%. HIF-1 α si -lencing significantly reduced the clonogenic activity and enhanced the radiosensitivity of Hep 3b cells with a SER of2.18. Conclusion:Hypoxia can induce HIF-1 α expression. HIF-1 α si lencing can enhance the radiosen-sitivity of HCC.