Objective To investigate the expression levels of angiogenesis- related factors in various clinical stages of hepatitis B- related hepatocellular carcinoma( HCC) and their clinical significance. Methods Seventy patients with hepatitis B- related HCC who were admitted to our hospital from 2011 to 2013 were enrolled as subjects and divided into four groups according to the HCC staging criteria: very early HCC group( n = 18),early HCC group( n = 17),advanced HCC group( n = 18),and end- stage HCC group( n = 17). Eighteen healthy volunteers were used as controls. The Luminex 200 liquid suspension array system was used to determine the expression levels of vascular endothelial growth factor( VEGF),vascular endothelial growth factor receptors( VEGFR- 1 and VEGFR- 2),and hepatocyte growth factor( HGF) in each clinical stage of hepatitis B- related HCC. Comparison of continuous data between two groups was made by t test. Results Compared with the control group,the very early HCC group had significantly higher levels of VEGF and HGF( t = 2. 69,P = 0. 008; t =2. 18,P = 0. 002). The early HCC group had significantly higher levels of VEGF,VEGFR- 1,and HGF than the control group( t = 1. 73,P = 0. 01; t = 2. 03,P = 0. 009; t = 2. 54,P = 0. 008). The levels of VEGF,VEGFR- 1,and HGF were significantly higher in the advanced HCC group than in the control group( t = 1. 64,P = 0. 01; t = 4. 38,P = 0. 007; t = 4. 02,P = 0. 005). In the end- stage HCC group,the levels of VEGF,VEGFR- 1,VEGFR- 2,and HGF were significantly higher than those in the control group( t = 4. 37,P =0. 007; t = 20. 24,P = 0. 009; t = 2. 21,P = 0. 01; t = 3. 06,P = 0. 003). Conclusion The levels of angiogenesis- related factors,VEGF and HGF,have already been substantially increased in the very early HCC,which induces a substantial upregulation of expression of VEGFR- 1 and VEGFR- 2 along with the progression of HCC.