Abstract: Objective To create the mice model of colorectal polyps with Apc-KRAS-Cre gene mutation with the best tamoxifen induction method. Methods C57CL/6J mice were used as healthy control group. Genetically mutated mice were grouped and intraperitoneally injected with tamoxifen of different concentration and dosage for different durations. The survival rate and change in weight of mice were observed. 4 weeks post-tamoxifen induction, mice were euthanized and the length of colons, amount and size of intestinal polyps were observed. Through H&E staining, the histopathological changes of the intestinal tissue and polyps were observed. Results The survival rate of male mice is higher than that of female mice(P<0.05), while the survival rate between the 4 groups shows statistical significance(P<0.05). When compared to the healthy control group, the changed in weight and the length of the colons of each group of mice showed statistical significance（P<0.001）, (P<0.05), the difference in weight change between group 1 and group 2, group 2 and group 3, group 1 and group 4; the difference in length of colons between group 1 and group 3 showed statistical significance (P<0.05). Each group of mice induced by tamoxifen injection showed intestinal polyps of varying sizes, mostly occuring on the distal end of the colon, while those in group 3 and group 4 have a higher amount and larger polyps. Comparing to healthy control group, histopathology of tamoxifen-induced mice showed growth of intestinal polyps, with uneven and misaligned glandular and epithelial arrangements, loosely-packed intestinal mucosal barrier and irregularly-distributed crypts, group 3 and group 4 mice showed signs of inflammation, while regions of group 4 showed necrosis of cells. Conclusion Tamoxifen-induced Apc-KRAS-Cre mice models have been successfully established, with group 3 induction method being the most suitable.