Primary cilia are antenna-like sensory organelles that transmit various extracellular signals. Ciliogenesis requires the removal of CP110 and its interactor CEP97 from the mother centriole for initiating ciliary axoneme extension, but the underlying mechanism remains unknown. Here we show that, upon serum starvation, CEP97 is partially degraded by the ubiquitin-proteasome system. CEP97 was polyubiquitylated in serum-starved cells, and overexpression of a non-ubiquitylatable CEP97 mutant effectively blocked CP110 removal and ciliogenesis induced by serum-starvation. Through several screening steps, we identified the cullin-3-RBX1-KCTD10 complex as the E3 ligase that mediates CEP97 degradation and removal from the mother centriole. Depletion of each component of this E3 complex caused aberrant accumulation of CEP97 on the centrosome, suppressed the removal of CEP97 and CP110 from the mother centriole, and impaired ciliogenesis. Moreover, KCTD10 was specifically localized to the mother centriole. These results suggest that CEP97 degradation by the cullin-3-RBX1-KCTD10 complex plays a crucial role in serum-starvation-induced CP110 removal and ciliogenesis.