Objective To explore the mechanism of 125I seed interstitial implantation-induced apoptosis of liver VX2 tumor cells in experimental rabbits, and to compare the effects of different radioactivity 125I seeds on the apoptosis and on the proliferation of tumor cells. Methods A total of 24 rabbit models with VX2 liver cancer were randomly and equally divided into 3 groups, and 125I seeds with different initial radioactivity were separately implanted into the rabbits of the three groups. 125I seeds of 0 mCi radioactivity were used in the control group (n=8), 125I seeds of 0.7 mCi radioactivity were used in the 0.7 mCi group (n=8) and 125I seeds of 1.0 mCi radioactivity were used in the 1.0 mCi group (n=8). The experimental rabbits were sacrificed at 5 weeks after the implantation; the tumor lesions were removed, and the effects of 125I seeds on the apoptosis and proliferation of tumor cells were determined. The tumor cell apoptosis rate, tumor growth-related factors, tumor growth factor expression protein and the influence of caspase-3 activity were evaluated. Results Regardless of their initial radioactivity, all the 125I seeds could make the tumor cell apoptosis rate increased, make Bcl-2 and VEGF expression level decreased, and make Bax expression increased, which were more obvious in 1.0 mCi group (P<0.05). The 125I seeds could increase the activity of caspase-3 within tumor tissue, but the difference between the 0.7 mCi group and the 1.0 mCi group was not significant (P>0.05). Conclusion The implanted 125I seeds can not only inhibit tumor’s growth through inducing apoptosis of tumor cells, but also inhibit tumor’s angiogenesis through influencing the expression of apoptosis-related gene and coding protein.