KRAS(KRAS Proto-Oncogene, GTPase) is a membrane-associated GTPase signaling protein that regulates proliferation, differentiation, and cell survival . Missense mutations at codons 12, 13, and 61 lock the protein in its GTP-bound form thus permitting its constitutive interaction with andactivation of multiple effectors , which promoting effects on cell proliferation and cell survival. Mutations of KRAS are found in a variety of human malignancies, including in pancreatic cancer, colorectal cancer, and non-small cell lung cancer at high frequency. However, no direct RASinhibitors exist for cancer therapy. To study the relationship between the mutational activation of KRAS and tumorigenesis, we established B6-Loxp-Stop-Loxp Kras G12D (B6-KrasLSL-G12D) strain. Floxed Stop sequences will be deleted in the mouse genome when Cre recombinase exists, oncogenic KRAS G12Dproteinare expressed with endogenous levels following removal of the stop cassette, which allows tocontrol of the timing, location, and the multiplicity of tumor initiation. When B6-KrasLSL-G12Dmice crossed with B6-Lyz2 Cre mice(expressing Cre recombinase in myeloid cell lineage andlung), the offspring mice were developed lung tumor with inflammatory cell infiltration at 6weeks age. When B6-KrasLSL-G12D mice crossed with B6-Alb Cre mice (expressing Cre recombinase in liver and lung ), the offspring mice (at 36 weeks age) were developedhepatobiliary cancer and the whole liver was covered with tumor tissue. B6-KrasLSL-G12D mice model can be used to study the occurrence and development of cancer.