Altogether, the findings of this study elucidate the impact of dynamic protein changes, particularly STAT1, in the host spleen during malaria and provide a research basis for developing therapeutic interventions for malaria.IMPORTANCEThe cumulative findings demonstrate the pathogenic role of STAT1 in host spleen during <i>Py</i>17XL parasite infection, highlighting its role in promoting IFN-γ production and exacerbating malarial anemia. The gene discussed is IFNG; the disease is parasitic infectious disease.