This project contains the mass spectrometry-based proteomic dataset generated for the study “Serological Characterization of CETP, PTPRZ1, and CPN2 Associated with Immune Infiltration in Lung Adenocarcinoma Revealed by a Tandem Mass Tag-Based Quantitative Proteomics Approach.” The study aimed to identify serum protein biomarkers associated with lung adenocarcinoma (LUAD) using tandem mass tag (TMT)-based quantitative proteomics. Serum samples from patients with early-stage lung adenocarcinoma and healthy controls were subjected to protein extraction, tryptic digestion, TMT labeling, peptide fractionation, and LC-MS/MS analysis. The labeled peptides were analyzed using an Easy-nLC system coupled to a Q Exactive HF-X mass spectrometer. The raw mass spectrometry data were processed using Proteome Discoverer and Mascot for peptide and protein identification, followed by quantitative and differential expression analyses using Perseus and R. This dataset includes the raw LC-MS/MS files and related processed identification and quantification files generated from the TMT-based serum proteomic analysis. Differential proteomic profiling identified 33 differentially expressed proteins between lung adenocarcinoma patients and healthy controls. Among these proteins, CETP, PTPRZ1, and CPN2 were selected for further clinical validation and bioinformatics analyses because of their differential expression patterns and potential relevance to diagnosis, prognosis, immune infiltration, and therapeutic response in lung adenocarcinoma. The deposited data are provided to support transparency, reproducibility, and further reuse of the proteomic analyses reported in this study.