Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by degeneration of dopaminergic neurons in the substantia nigra. alpha-synuclein (alpha-syn) and PTEN-induced putative kinase (PINK) 1 are two critical proteins associated with the pathogenesis of PD. alpha-syn induces mitochondrial deficits and apoptosis, PINK1 was found to alleviate alpha-syn-induced toxicity, but the mechanistic details remain obscure. Here, we show that PINK1 interacts with a-syn mainly in the cytoplasm, where it initiates autophagy. This interaction was dependent on the kinase activity of PINK1 and was abolished by deletion of the kinase domain or a G309D point mutation, an inactivating mutation in the kinase domain. Interaction between PINK1 and alpha-syn stimulated the removal of excess alpha-syn, which prevented mitochondrial deficits and apoptosis. Our findings provide evidence for a novel mechanism underlying the protective effects of PINK1 against a-syn-induced neurodegeneration and highlight a novel therapeutic target for PD treatment.