Background/Aims: When hepatocellular carcinoma (HCC) is exposed to hypoxic condition, HIF-1α is activated and results in angiogenesis and increased tumor burden. Although inhibition of HIF-1α may reduce tumor growth, there are some limitations to control tumor growth completely. For a more effective therapy for HCC, we investigated HIF-1α independent pathway related tumor growth with angiogenesis. Methods: We cultured HepG2 cells (HCC cell line) in both normoxia and hypoxia conditions. These cells were divided into three groups: a echinomycin treated group, a echinomycin and quinazoline treated group and a control group without any treatments. Growth morphologies of cells were observed with a microscope after 24 hours. Immunocytochemistry assay was done to detect the angiogenesis during inhibition of HIF-1α and/or NF-κB in hypoxia condition, and compared with results in normoxia condition. Results: In normoxia, the expression of HIF-1α on tumor growth was not found. In hypoxia, inhibition of HIF-1α reduced the tumor growth compared to the control group. But, inhibition of both HIF-1α and NF-κB did not show apparent reduction of tumor growth as shown in HIF- 1α only group. Conclusions: Signaling pathways related to cancer cell growth exist through a vast network. Inhibition of one target molecule may result in over-expression of other molecules related to the tumor growth. For an effective therapy in blocking of the tumor growth, more comprehensive understanding of the network related to signaling pathways on tumor growth is necessary. (J Liver Cancer 2016;16:31-37)