This dataset presents quantitative proteomics profiling of Colon tissues derived from young mice (3-week-old) challenged with H1N1 influenza virus, alongside age-matched mock-infected controls. Using Data-Independent Acquisition (DIA) Quantitative Proteomics Technology, we systematically identified and quantified differentially expressed proteins (DEPs) in response to H1N1 infection at 2 days post-inoculation.