This study reports that Aurora-A (Aur-A) phosphorylates Fas-associated factor-1 (FAF1) at Ser-289 and Ser-291. Forced expression of a FAF1 mutant mimicking phosphorylation at Ser-289 and Ser-291 (FAF1 DD), but not phosphorylation-deficient FAF1 (FAF1 AA), reduced Aur-A expression. However, transfection of FAF1 DD failed to reduce Aur-A expression in the presence of MG132 and MG115, indicating that this decrease is proteasome-mediated. Additionally, transfection of FAF1 DD suppressed the expression of Aur-A in ts20-BALB cells lacking E1 ubiquitin (Ub) activating enzyme activity at restrictive temperatures and also reduced the expression of Aur-A S51D, a mutant resistant to Ub-dependent degradation. Our data indicate that phosphorylated FAF1 mediates the ubiquitin-independent, proteasome-dependent degradation of Aur-A. Overexpression of FAF1 DD blocked Aur-A-induced centrosome amplification and accumulated cells in G(2)/M phase, representing cellular phenotypes consistent with the anticipated loss of Aur-A. Collectively, our findings support the negative feedback regulation of Aur-A via phosphorylation of the death-promoting protein, FAF1, and disclose the presence of molecular cross-talk between constituents of the cell cycle and cell death machinery.