To investigate the expression and clinical significance of Notch3, LGR5and NF-κB in colorectal adenocarcinoma.Methods The expression of Notch3, LGR5 and NF-κB in 54 colorectal adenocarcinoma tissue, 30 colorectal adenoma tissue and 12 normal colorectal mucosa tissue were detected by immunohistochemistry.Results The positive rates of Notch3, LGR5 and NF-κB in normal colorectal tissue group, adenoma group and adenocarcinoma group were gradually increasing.Their positive expression rates in colorectal adenocarcinoma group were 63%(34/54), 57.4%(31/54) and 63%(34/54), respectively, significantly higher than that of normal group (8.3%, 16.7%, 25%) (P＜0.05) and adenoma group (26.7%, 36.7%, 30%).There was no significant difference between the adenoma group and the normal group (P＞0.05).The above indicators weren't correlated with age, gender, tumor site, degree of differentiation and the diameter of tumor(P＞0.05).The expression of Notch3, LGR5 and NF-κB in colorectal adenocarcinoma were all related to lymph node metastasis and Dukes stage(P＜0.05).Notch3 and NF-κB were also related to the tumor infiltration depth(P＜0.05).Notch3 was positively correlated with LGR5's expression in colorectal adenocarcinoma (r=0.325, P＜0.05).Conclusion Notch3, LGR5 and NF-κB may be involved in the occurrence and development of colorectal adenocarcinoma