Abstract: Objective: To investigate the expression levels of serum miR-638 in the patients with breast cancer and its clinical value. Methods: One hundred and fifty-two patients with breast cancer were selected as the disease group, and 102 healthy persons as the control group. The expression levels of miR-638 in their serum samples were detected by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the expression levels of serum miR-638 in the patients with different pathological stages, before and after operation, and before and after chemotherapy were compared. The diagnosis efficacy of serum miR-638 alone and in combination with CEA, CA125, CA15-3 for breast cancer was analyzed by the ROC curve and Z test. Results: The expression levels of serum miR-638 in the breast cancer group (3.6 [1.3～10.5]) were significantly lower than that in the control group (79.0 [52.5～120.8],P＜0.01). The linear regression analysis showed that chemotherapy and pathological staging were the main factors influencing the expression levels of serum miR-638. The area under the ROC curve (AUC^ROC) of serum miR-638 in the diagnosis of breast cancer was 0.954. When the cut-off value of serum miR-638 was 27.47, its sensitivity and specificity for the diagnosis of breast cancer were 94% and 86.2%, respectively. The area under the ROC curve (AUC^ROC) of serum miR-638 combined with CEA, CA125 and CA15-3 in the diagnosis of breast cancer was 0.978 8. When the combined cut-off value was 0.29, their sensitivity and specificity for the diagnosis of breast cancer were 95.4% and 89.5%, respectively. There was no significant difference in the AUC^ROC between miR-638 alone and combined screening (Z=1.68,P=0.091). Conclusion: Serum miR-638 may be a potential molecular marker for the screening of breast cancer.