This dataset contains quantitative proteomics data obtained from a mouse model of PD-1 resistance in microsatellite instability-high (MSI-H) colorectal cancer. Using Data-Independent Acquisition (DIA) mass spectrometry, protein samples were analyzed to identify differentially expressed proteins between PD-1-sensitive and PD-1-resistant tumor samples. The data were acquired using high-resolution mass spectrometry on a Thermo Scientific Orbitrap instrument, followed by protein identification and label-free quantification (LFQ) using DIA-NN software. The dataset includes protein identification and quantification results from various tumor samples, with a focus on identifying key proteins involved in immune evasion mechanisms that contribute to resistance to αPD-1 immunotherapy. Differential protein expression analysis revealed several proteins that are significantly upregulated or downregulated in PD-1-resistant tumors, which may serve as potential biomarkers or therapeutic targets.