In this study, we used TGFβ1 siRNA and modified LNPs with altered PEG derivatives (CE1.5 TGFβ1 siRNA LNP, CE2.5 TGFβ1 siRNA LNP, and TPGS2.5 TGFβ1 siRNA LNP; abbreviated as CE1.5 LNP, CE2.5 LNP, and TPGS2.5 LNP) to observe whether they can effectively accumulate in the tumor site, as well as their efficacy and safety on the treatment of paclitaxel-resistant lung adenocarcinoma, and we further explored the impact of these PEG derivatives on LNPs. This evidence concerns the gene TGFB1 and lung adenocarcinoma.