Objective To reprogram human hepatocellular carcinoma cell Huh7 into pluripotent stem cells. Methods Four recombinant lentiviruses individually carrying Oct4, Sox2, Nanog, and Lin28 were constructed and used to co-infect Huh7 cells in vitro. Post infection, the obtained pluripotent stem-like cells were identified by Alkaline phosphatase staining, immunofluorescence assay, quantitative-PCR and immunohistochemistry. The differentiation capability of the cells was examined by teratogencity test. Results Pluripotent stem-like cell colonies (iHuh7) were observed in cultured Huh7 cells after lentivirus-based induction. These colonies were positive for alkaline phosphatase staining and immunofluorescence assay showed expression of pluripotent factors: Oct4 and TRA-1-60. Quantitative-PCR indicated that several endogenous pluripotency-associated genes and stem cell-specific microRNAs were highly expressed in these pluripotent stem-like cells. In vivo differentiation test showed that iHuh7 cells could lead to teratogencity. ConclusionHuh7 cells can be induced into pluripotent stem-like cells mediated by lentiviruses individually carrying Oct4, Sox2, Nanog, and Lin28.