BACKGROUND: The World Health Organization has mentioned breast cancer holds the highest incidence rate among all types of cancer globally. Death-associated protein kinase 2 (DAPK2) is a serine/threonine kinase linked to various forms of malignancy, such as breast cancer. This protein assumes a pivotal function in a multitude of cellular mechanisms, including apoptosis, autophagy, and cell migration. AIMS: This study aimed to study the LOC101928988 regulatory effect on the DAPK2 expression in breast cancer. METHODS: In this study, 38 paired tumoral and normal tissues were selected from patients. Quantitative real-time PCR was used to analyze the expression of DAPK2 and LOC101928988. The interactions of DAPK2 and its intermediate elements with LOC101928988 were predicted by docking analysis. RESULTS: The expression of DAPK2 and LOC101928988 was downregulated in tumor tissues compared to the control group. Further analysis revealed a significant positive correlation between DAPK2 and LOC101928988 levels in tumoral and adjacent normal tissues. A comparison of gene expression between different grades, stages, and HER2 statuses showed significant findings. ROC curve analysis of DAPK2 and LOC101928988 expression revealed 77% and 72% AUC for BC tissue, respectively. CONCLUSIONS: Overall, our results suggest that alterations in the levels of DAPK2 and LOC101928988 may be involved in tumor initiation and progression in breast cancer. It has also been reported that LOC101928988 probably has a role in regulating DAPK2 expression through interaction with transcription factors.