Objective: To discuss the expression of CD147 [extracellular matrix metalloprotein inducer (EMMPRIN)] mediated by specific protein (SP1), the activation of hypoxia inducible factor-1α (HIF-1α), and the effect of vascular endothelial growth factor (VEGF) signaling pathway on angiogenesis in ovarian cancer. Methods: The angiogenesis is the critical step in tumorigenesis. Most malignant tumors have dense angiogenesis and grow fast, which is due to the tumor cells can secrete many kinds of growth factors themselves to induce angiogenesis. Therefore, angiogenesis plays an important role in the development and metastasis of tumors and inhibition of it will significantly prevent the development and metastasis of tumor tissues. In vitro angiogenesis assay could simulate the procession of tumor angiogenesis well. In this study, the experiment was divided into overexpression group (OE group), silencing group (SI group), CONTROL group (CONTROL group), and neg. CONTROL group (NC group). By silencing or over-expressing of SP1 or CD147 in ovarian cancer cell line SKOV3, blocking HIF-1α/VEGF signal pathway with HIF-1α protein translation inhibitor KC7F2, and then using culture supernatants to act on human umbilical vein endothelial cells (HUVEC-12), in vitro angiogenesis assay was carried out to simulate tumor angiogenesis changes. Meanwhile, fluorescence real-time quant. PCR (RT-qPCR) was used to examine the expressions of CD147 and VEGF in the cells. Results: The amount of vascular arborizations in NC group (206.33±16.03) was more than that in SI-CD147 group (137.00±15.09). The mRNA level of CD147 in OE-SP1 group (2.38±0.26) was higher than that in SI-SP1 group (0.55±0.12). The amount of vascular arborizations in SI-SP1+OE-CD147 group (200.00±19.52) was more than that in SI-SP1 group (130.00±12.01). The amount of vascular arborizations in OE-CD147 group (373.67±29.02) was more than that in OE-CD147+KC7F2 group (187.00±19.52). The mol. level of VEGF in OE-CD147 group (4.05±0.09) was higher than that in OE-CD147+KC7F2 group (1.02±0.11). Conclusion: The expression of CD147 increases in ovarian cancer, and the upstream transcription factor SP1 is able to upregulate the expression of CD147, thereby activating HIF-1α/VEGF signaling pathway to promote the angiogenesis of ovarian cancer, and ultimately leading to the pathogenesis of ovarian cancer.