Objective To approach the inhibitory effect of Iodine-125 (125I) on moderately differentiated adenocarcinoma of colon by establishing the nude mice model bearing subcutaneous tumor of SW480 cell. Methods The moderately differentiated adenocarcinoma of colon cells (SW480) were implanted subcutaneously to the nude mice. The bearing tumor nude mice were randomly divided into study group (n=24) and control group (n=24) by using method of random sampling. One blank particle was implanted into the mouse of the control group, a 1.48×107 Bq dosage 125I particle was implanted into the mouse of the study group, then the growth of tumor was observed after implantation. Six bearing tumor nude mice were sacrificed and the tumors were obtained on day 7, 14, 21, and 28 after implantation, respectively. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry SP method. The cell apoptosis was determined by TUNEL method. Results As the accumulation of radiation time, the volume of tumor in the study group was smaller than that in the control group on day 10 after implantation (Plt;0.05). The PCNA labeling index in the study group was lower than that in the control group on day 14 after implantation (Plt;0.05). The apoptotic index in the study group was higher than that in the control group on day 21 after implantation (Plt;0.05). Conclusion Persistent low dose 125I radiation could down-regulate the expression of PCNA, and induce the apoptosis of moderately differentiated adenocarcinoma of colon cell, which might be a mechanism of inhibiting the proliferation of moderately differentiated adenocarcinoma of colon.