Fibroblast growth factor binding protein 1 (FGFBP1) is expressed in various tumors and may serve as a diagnostic marker and/or a therapeutic target. Previous studies suggested FGFBP1 functions as an angiogenic switch molecule by regulating the activity of FGF2, and it was later found to associate with a broad spectrum of FGFs. To study FGFBP1, we used zebrafish, in which the function of extracellular matrix protein can be easily studied in intact tissues or organisms. When Fgfbp1 expression was knocked down, morphants manifested massive cell death and structural abnormalities. Cell death was most prominent in the brain and the neural tube, but not limited to those regions. These findings suggest that the primary function of Fgfbp1 may be to sustain cellular survival throughout embryogenesis. For comparison, the expression of fgf2 was limited to the early stage of embryogenesis and fgf2 morphants showed more severe phenotype, with high morbidity before reaching 14-somites. Taken together, our work reveals the physiologic function of Fgfbp1, and that its function could be exerted in a Fgf2-independent manner.