The recent remarkable success of mesoporous silica nanoparticle (MSN) technology has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. However, as an anti-tumor drug delivery system, traditional MSN is prone to clearance by the host immune system, resulting in suboptimal pharmacokinetics and inadequate drug concentrations in tumors. The emergence of biomimetic drug delivery systems has effectively addressed these challenges. In this study, we aimed to develop a biomimetic drug delivery system based on MSN to achieve both immune evasion and tumor targeting. To this end, we coated folic acid-modified mesoporous silica (FMSN) cores with lipid-hybridized macrophage membranes (HEs) through co-extrusion, yielding FMSN@HEs. Initially, we demonstrated effective retention of key proteins Integrin α4 and Integrin β1 in the HEs, leading to significantly reduced clearance of FMSN@HEs by phagocytes in vitro. CCK-8 experiments validated the ability of CUR-FMSN@HEs to effectively inhibit the proliferation of tumor cells. In tumor-bearing mice, FMSN@HEs exhibited stronger tumor targeting and penetration abilities compared to MSN without HEs. The immune escape and tumor-targeting properties of the FMSN@HEs suggest that they could be used as novel bionic drug carriers, potentially providing more options for antitumor therapy.