The subcutaneous xenograft model with co‐implantation of HSCs and OE‐cPKM HCCC‐9810 cells was established to further verify if LNPs inhibited myofibroblast activation of HSCs by delivering si‐cPKM, thereby reducing fibrosis and causing collapsed microvessel opening in ICC tumors. The gene discussed is CKM; the disease is intrahepatic cholangiocarcinoma.