Objective To observe the expression of CD15 antigen, CD44v6 protein and matrix metalloproteinase-3 (MMP-3) in breast cancer and analyze their correlation. Methods Totally 80 cases of breast cancer patients from July 2014 to July 2016 admitted to our hospital diagnosis and treatment were selected as the research object, and the expression level and difference of CD15 antigen, CD44v6 protein and MMP-3 were detected by immunohistochemistry in tumor tissues and adjacent tissues. Results The total positive rate of CD15 antigen, CD44v6 protein and MMP-3 in tumor tissues was higher than those in adjacent tissues, and the difference between the two groups was statistically significant (P < 0.05). The expression of CD15 antigen, CD44v6 protein and MMP- 3 in breast cancer tissues were positively correlated with lymph node metastasis and histological grade (P < 0.05), but had no significant correlation with the age and menopause (P > 0.05). The expression of CD15 antigen, CD44v6 protein and MMP-3 in breast cancer tissues were positively correlated (P < 0.05). Conclusions The expression of CD15 antigen, CD44v6 and MMP-3 protein in breast tumor tissue has a certain relevance. The expression of CD15 antigen, CD44v6 and MMP-3 protein has important reference value to degree of invasion and malignant lesions in the differential diagnosis of breast tumor.