Objective:To investigate the expression and clinical significance of plasma miR-221 in patients with breast cancer. Methods: The expressions of plasma miR-221 in 20 cases of healthy volunteers and 56 patients with breast cancer were detected by real-time RT-PCR as well as miR-221 expression in 56 breast cancer and their matched non-tumor adjacent tissues; The relationship between plasma miR-221 expression and clinicopathological characteristics and drug resistance were further analyzed using statistical methods, including independent-samples t test, multiple logistic regression analysis. Results: The expression of plasma miR-221 in patients with breast cancer was significantly higher than that of the healthy volunteers (P < 0.05); The expression of plasma miR-221 in patients with breast cancer was positively correlated with miR-221 expression in breast cancer tissues (r=0.832, P < 0.001); Before the therapy, the expression of plasma miR-221 in breast cancer patients was positively correlated with lymph nodes metastasis and clinical stages, while it was positively correlated with drug resistance only after chemotherapy. Conclusion: MiR-221 highly expressed in plasma of patients with breast cancer reflecting the expression level of miR-221 in breast cancer tissues. The expression of miR-221 in plasma could be used as one of the indicators for clinical stages and the drug resistance.