Objective: To explore the effect and mechanism of LncRNA HIF1A-AS2 on osteogenic differentiation and angiogenesis of bone marrow mesenchymal stem cells. Methods: The experiment cells was divided into six groups: Control group, Osteogenic group, LncRNA HIF1A-AS2 NC1 group, LncRNA HIF1A-AS2 overexpression group, LncRNA HIF1A-AS2 NC2 group, and LncRNA HIF1A-AS2 interference group. LncRNA HIF1A-AS2 overexpression vector and interference vector HIF1A-AS2-shRNA1, HIF1A-AS2-shRNA2, HIF1A-AS2-shRNA3 constructed in vitro were transfected into osteogenic differentiation of hMSC cells, and the transfection efficiency was detected by RT-PCR. Cell viability was detected by CCK-8 and cell apoptosis was detected by flow cytometry. Alizarin red staining was used to observe the calcification deposition of cells in each group. The expression levels of HIF1A-AS2, MMP2 and VEGF165 mRNA were detected by RT-PCR, and the protein expression levels of MMP2 and VEGF165 were detected by Western blot. Results: Overexpression of LncRNA HIF1A-AS2 promoted cell proliferation and inhibited apoptosis. A large number of red calcified nodules were deposited after alizarin red staining. The mRNA and protein expression levels of MMP2 and VEGF165 in the LncRNA HIF1A-AS2 overexpression group increased significantly (P<0.01), and the expression of the LncRNA HIF1A-AS2 interference group decreased significantly (P<0.01). Conclusion: LncRNA HIF1A-AS2 can promote cell proliferation, inhibit cell apoptosis, and promotes the differentiation of hMSC cells into osteoblasts. Overexpression of LncRNA HIF1A-AS2 can increase the expression levels of MMP2 and VEGF165 and stimulate osteogenic differentiation and angiogenesis, providing a new strategy for clinical application to accelerate bone tissue regeneration.