〔Abstract〕 Objective To investigate the effect of lentivirus mediated silencing ofNIPBLgene on osteogenic differentiation of mouse bone marrow mesenchymal stem cells(BMSCs). Methods The third generation C57 Mouse Bone marrow mesenchymal stem cells were divided into experimental group, negative control group and blank control group. The lentiviral vector was transfected into mouse bone marrow mesenchymal stem cells, the transfection results were observed by inverted fluorescence microscope, and the expression ofNIPBLgene was detected by real-time PCR. The cells of each group were cultured by osteogenic induction. The alkaline phosphatase activity was detected. Real-time PCR and Western blot were used to measure the mRNA and protein expression ofOCN,BMP-2 andRUNX-2. Results The expression ofNIPBLmRNA decreased in the experimental group(P<0.05). The activity of alkaline phosphatase in experimental group was lower than that in negative control group and blank control group(P<0.05). The gene transcription and protein expression levels ofOCN,BMP-2 andRunx-2 in experimental group were lower than those in negative control group and blank control group(P<0.05). Alizarin red staining results showed that the negative control group and blank control group had more red calcium nodules than the experimental group. Conclusion Lentivirus mediated silencing ofNIPBLgene reduces the proliferation of mouse bone marrow mesenchymal stem cells, inhibits the expression of osteogenic differentiation related genes, and reduces the osteogenic differentiation ability.