Objective To determine whether the cytokeratin 19 (CK19) positive (CK19⁺) cells in mouse liver have the potential of differentiation into mature hepatocytes. Methods The CK19^CreERT/Rosa26-GFP double-transgenic mice were obtained by hybridizing CK19^CreERT mouse with Rosa26-GFP mouse and the GFP-labeled CK19⁺ cells were observed in mouse liver after tamoxifen (TM) injection. Then we constructed the 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC)-induced liver injury mouse model and carbon tetrachloride (CCl₄)-induced liver injury mouse model in CK19^CreERT/Rosa26-GFP double-transgenic mouse and determined the differentiation potential of GFP-labeled CK19⁺ cells by frozen sections and immunofluorescence staining of liver tissues. Results The CK19^CreERT/Rosa26-GFP double-transgenic mice were obtained and the CK19⁺ cells were genetically labeled with GFP after TM injection. In DDC model, we detected GFP⁺ cholangiocytes in proliferating ductules, in which CK19, a marker for biliary epithelial cells was expressed, and the proportion of GFP⁺ cholangiocytes in the DDC model group ([63.5±6.3]%) was significantly higher than that in the control group ([53.6±4.8]%, P<0.05). In CCl₄ model, we identified GFP⁺ hepatocytes in the liver parenchyma; we also found that the hepatocyte-specific marker albumin was expressed in the GFP⁺ hepatocytes; and the proportion of GFP⁺ hepatocytes in the CCl₄ model group ([0.15±0.02]%) was significantly higher than that in control group ([0.008±0.003]%, P<0.01). Conclusion There are liver stem cells with a potential for hepatic differentiation in the CK19⁺ cells in mouse liver, which may provide a new clue for the identification of liver stem cells.