Influenza A virus (IAV) infection induces profound alterations in host protein expression that dictate viral pathogenesis and host immune outcomes. To systematically trace dynamic host protein alterations during acute infection, we conducted a quantitative proteomic study on lung tissues from female BALB/c mice (6~8weeks old, n = 5 per group) intranasally infected with 10*LD50 of a mouse-adapted H1N1 strain (mH1N1). Lung tissue samples were harvested across a time-course of infection (0, 1, 3, and 5 days post-infection [dpi]) and analyzed via Data-Independent Acquisition mass spectrometry (DIA-MS). Over 9,000 host proteins were quantified per sample group. Differential expression analysis identified significant time-dependent proteomic changes, highlighting robust activation of innate immune defense, cytokine-mediated signaling, and neutrophil activity alongside dynamic remodeling of cell structures and metabolic pathways. Overall, this study establishes a comprehensive temporal host proteome landscape during lethal IAV infection, providing critical molecular targets for understanding IAV pathogenesis and developing antiviral strategies.