Purpose: Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death among women worldwide. Early detection, treatment, and metastasis monitoring are very important for the prognosis of BC patients. Therefore, effective biomarkers need to be explored to help monitor the prognosis of BC patients and guide treatment decisions. Methods: In this study, the relationship between CCDC69 expression levels and tumor clinical characteristics were analyzed using RNA-seq information in BC samples from the TCGA database. Kaplan-Meier survival analysis was performed to analyze the prognostic value of CCDC69 in BC patients. Besides, gene enrichment analysis in BC samples was used to confirm the main function of CCDC69 in BC. The correlation between the expression of CCDC69 and the number of tumor-infiltrating lymphocytes was confirmed by interaction analysis of TIMER and GEPIA. Results: The results showed that CCDC69 expression was significantly lower in cancer samples than in normal tissues, and was significantly lower in highly invasive BC than in carcinoma in situ. Meanwhile, low levels of CCDC69 were associated with a further poor prognosis. CDCC69 expression was positively correlated with the amount of different tumor-infiltrating lymphocytes. Mechanically, it could be presumed that the low expression of CCDC69 in BC might be caused by hypermethylation of the promoter region. Conclusions: Summarily, CDCC69 could be used as a potential biomarker to predict the prognosis of BC and the sensitivity to immunotherapy such as PD-1/PD-L1 checkpoint inhibitors.