Provide a safer way for treating various cancers with PLGA-PEG-PLGA (PPP)-embedded iodine-125. To improve the safety of iodine treatment for colon cancer, iodine-125 solution was embedded into PLGA-PEG-PLGA (PPP) (synthesized by bulk co-polymerization of dl-polylactide glycolide and PEG). Xenograft-carrying nude mice were then treated with iodine-125-PPP. Proliferating cell nuclear antigen and Terminal Transferase dUTP Nick-End Labeling were used to measure proliferation and apoptosis in the tumors, respectively. Simultaneously, immunohistochemistry SP was used to detect the expression levels of p53. In addition, the microvessel density (MVD) of the tumors was recorded. PPP-embedded iodine-125 induced apoptosis by increasing the expression of p53, and by decreasing the levels of VEGF and MVD in the colon cancer tumors (P < 0.01). Significant inhibition of tumor growth is seen with iodine-125 from 0.4 to 0.8 mCi. PPP-embedded iodine-125 has a similar inhibitory efficiency to using the iodine-125 seeds for the treatment of colon tumors (P > 0.05). The findings therefore provide a potentially safer method for treating various tumors with radioactive iodine.