Objective:To discuss the effects of Xiaotan Tongfu (XTTF) Decoction on protein expression of nuclear factor-κB(NF-κB)/ interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3)and activation induced cytidine deaminase(AICD)in colorectal mucosal epithelium of mice with colorectal precancerous lesions model. MethodsAccording to the random number table,ninety C57BL/6 mice were randomly divided into five groups:the control group,model group,western medicine group(Sulfasalazine group), traditional Chinese medicine group(XTTF Decoction group)and the combination group(Sulfasalazine and XTTF Decoction group). Except the control group,model was established in the other four groups by the AOM/DSS “four-step three-cycle method”. General condition of mice and pathological changes of colorectal mucosa epithelium in each group were observed. The rate of tumor formation of colorectal precancerous lesions was calculated. The protein expression of NF-κB/IL-6/STAT3 and AICD in colorectal mucosal epithelium of mice during the modeling process (6 weeks,14 weeks,18 weeks) were detected by Western Blotting.  Results:After the treatment of XTTF Decoction,the general condition of mice were better than the mice in the model group. The rate of tumor formation in the combination group (33.33%) was lower than that in the model group (50.00%). After treatment for 14 and 18 weeks,compared with the western medicine group,the changes of NF-κB expression in the traditional Chinese medicine group and combination group were not significant,but the expression levels of IL-6,STAT3 and AICD were all significantly down-regulated. Compared with the traditional Chinese medicine group, the differences on the expression of IL-6 and STAT3 in the combination group were not significant,but the AICD expression was significantly lower than that in the traditional Chinese medicine group.  Conclusion: XTTF decoction can improve the general condition of mice with colorectal precancerous lesion,decrease the incidence of colorectal precancerous lesions,down-regulate the protein expression of IL-6/STAT3 as well as AICD in colorectal mucosal epithelium. This may be one of its mechanisms on decreasing the incidence of colorectal precancerous lesions and preventing the occurrence of colorectal cancer.