Fibroblast growth factor receptor 1 (FGFR1) plays roles in angiogenesis, wound healing, and embryonic development via the regulation of cell proliferation, differentiation, and survival. It is well known that ectopic expression of FGFR1 is associated with cancer development. To characterize the function of FGFR1 in the normal and cancer cell lines DF-1 and DT40, respectively, we performed FGFR1 knockdown by RNA interference. In the DT40 cells, FGFR1 knockdown induced upregulation of FGFR2 and FGFR3 expression, downregulation of pro-apoptosis-related genes, and upregulation of anti-apoptosis-related genes. However, in DF-1 cells, FGFR1 knockdown induced upregulation of pro-apoptosis-related genes and downregulation of anti-apoptosis-related genes. Our data suggest that repression of FGFR1 induced upregulation of other FGF receptors and anti-apoptosis-related genes in cancer cells and pro-apoptosis-related genes in normal cells.