The tumor suppressor p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis. Here, we identify nerve growth factor receptor (NGFR, p75NTR, or CD271) as a novel negative p73 regulator. p73 activates NGFR transcription, which, in turn, promotes p73 degradation in a negative feedback loop. We demonstrate that NGFR directly binds to p73’s central DNA binding domain and suppresses p73 transcriptional activity and p73-mediated apoptosis in cancer cells. We uncover a previously unknown mechanism of p73 degradation through the chaperonemediated autophagy (CMA) pathway, and establish NGFR as a key mediator. Collectively, our studies demonstrate a new oncogenic function for NGFR in inactivating p73 activity by promoting its degradation through the CMA.