We performed 4D-DIA proteomic profiling on formalin-fixed paraffin-embedded (FFPE) thyroid tissues, covering anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma (PTC), and matched normal (N) controls. Using the timsTOF Pro platform with ion mobility–enhanced DIA, we systematically quantified global protein expression across tumor subtypes. The dataset provides high-quality spectral data and processed protein quantitation matrices, enabling comparative analyses of thyroid cancer progression from differentiated to undifferentiated states. This resource supports biomarker discovery and mechanistic exploration in thyroid cancer biology.