Abstract: Objective To analyze the depressive state of breast cancer patients, investigate its correlation with the expression of related genes and the practical implications for clinical practice. Methods From January, 2015 to December, 2016, a total of 112 female patients diagnosed with breast cancer were selected as the subjects. Age was 32-68 years old, the average age was (48.0 ±5.5) years. To evaluate the patients' depression using the Hamilton Depression Scale (HDMD), according the results all the patients were divided into depression group and non-depression group. Using the method of real-time fluorescent quantitative PCR detection, analysis and purificate the total mRNA of cells, and compared with the differences between the two groups in the expression of microRNA-320 a, microRNA-17-5 p, microRNA-223-3 p, microRNA-451 a, microRNA-223, microRNA-452 gene protein. The correlation between depression and depression was analyzed. Results The HAMD score in the depressive patients was (13.7 ±1.6) scores, it was significantly higher than that in the non-depressive patients[(3.6 ±1.1) scores] (t=39.516, P<0.05). Compared with the differences between the two groups in the expression levels of microRNA-320 a, microRNA-451 a and microRNA-223, it was statistically significant (statistic value Z were respectively 6.252, 5.183, 7.904, all P<0.05). Pearson correlation analysis results showed that in breast cancer patients the depression status was related to age distribution (R=0.420, P=0.040), clinical stage (R=0.610, P=0.013), and the gene expression changes of microRNA-320 a (R=0.500, P=0.023), microRNA-451 a (R=0.430, P=0.034), microRNA-223 (R=0.660, P=0.010) and other. Conclusion The clinic could monitore the HAMD score, and pay attention to the expression of microRNA-320 a, microRNA-451 a, microRNA-223 and other microRNA expression, it can be used to evaluate the depressive state of breast cancer patients, and provide guidance for the later treatment.