This dataset includes mass spectrometry-based proteomic profiles of cisplatin-resistant (cisR) and cisplatin-sensitive (cisS) MDA-MB-231 triple-negative breast cancer (TNBC) cell lines. The study aimed to investigate the molecular alterations contributing to cisplatin resistance using data-independent acquisition (DIA) proteomics. Key findings revealed upregulation of extracellular matrix (ECM) remodeling proteins (e.g., COL6A1, COL6A3), drug efflux transporters (e.g., ABCC4), and membrane-associated resistance proteins (e.g., TIMP1, MMP-14, APP), highlighting their potential roles in chemoresistance. The data provide insights into resistance-associated signaling, metabolic pathways, and potential therapeutic targets in TNBC.