In summary, this study highlighted some anticancer aspects of sFLT01 as a next-generation antiangiogenic agent and showed that the inhibitory impact of sFLT01 on angiogenesis, growth, invasiveness, and migration of cancer cells could be mediated through the modulation of VEGF/GRP78/MMP2&9 axis and activation of TIMPs. This evidence concerns the gene HSPA5 and cancer.