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IQ motif containing GTPase activating protein 1 (IQGAP1) is a protein scaffold that integrates signals regulating various cellular functions. Recently, utilizing proteomics as a discovery tool and co-immunoprecipitation as a validation method, we reported IQGAP1 as a potential ligand for CD11c, an adhesion molecule that was highly expressed in the intracellular components of neutrophils and regulated the maturation, survival, and function of neutrophils. To date, the role of IQGAP1 in inflammation and immune response is largely unknown. In this study, we reported the direct binding of CD11c with IQGAP1 through various methods. In addition, we investigated the role of IQGAP1 in neutrophil functions by using IQGAP1 knockout (KO) mice. We discovered that IQGAP1 deficiency led to impaired bone marrow neutrophil maturation, reactive oxygen species (ROS) generation, phagocytosis, and neutrophil extracellular traps formation. Thus, for the first time, we reported the essential role of IQGAP1 in neutrophil development.