〔Abstract〕 Objective To construct folate modified D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS) nanomaterials(FA-TPGS), which can stably load and effectively release siRNA, and to observe the effects of nanoparticles on the cytotoxicity and spliced X-box binding protein 1(XBP1s)of mouse leukemia cells of monocyte macrophage(RAW264.7). Methods Mixed FA-TPGS and rhodamine B(RhB) labeled XBP1 siRNA solution in a proportion of 5 ∶1 and obtained the nano-complex coated with XBP1 siRNA(FT@XBP1). FT@XBP1 nanocarriers were characterized by transmission electron microscope, dynamic light scattering, ultraviolet visible spectrum analysis and/or fluorescence analysis. And the release of siRNA from FA-TPGS nano-carriers was calculated simultaneously. The cell cytotoxicity of FT@XBP1 nanomaterials were detected by scanning electron microscopy(SEM), CCK-8 and flow cytometry. And the inhibited effect of XBP1s of RAW264.7 cells was checked by Western blot. Results FA modified TPGS could effectively bind XBP1 siRNA. And the average particle size of FT@XBP1 nanocarriers were(200±20)nm. The relative release assays showed that acidic environments(pH 5.0)was beneficial for siRNA to release from FT@XBP1. Both CCK-8 and apoptosis assay showed that the effects of FT@XBP1 on the proliferation and apoptosis of RAW264.7 cells were relatively small, and FT@XBP1 could significantly inhibit the expression of XBP1s protein in RAW264.7(P<0.001). Conclusion TPGS nanoparticles modified with folic acid can effectively encapsulate XBP1 siRNA and inhibit XBP1s expression of RAW264.7 cells with good cellular compatibility.