Serum response factor (SRF)， a transcription factor highly expressed in neurons， is involved in neuronal survival and the pathogenesis of some neurodegenerative disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons vulnerable to 1-methyl 4-phenyl 1，2，3，6-tetrahydropyridine-induced neurotoxicity， however， the underlying mechanisms remain poorly understood. Here， we report decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that was associated with the loss of tyrosine hydroxylase (TH)-positive neurons. SRF expression was also reduced in rotenone-treated PC12 cells in vitro. In addition， Srf knockdown augmented rotenone-induced toxicity in PC12 cells. In contrast， overexpression of Srf attenuated the cells' sensitivity to rotenone and alleviated rotenone-induced α-synuclein accumulation. The protective effect of SRF was abolished when the expression of autophagy-related proteins Beclin 1 and Atg5 was suppressed. These results suggested that SRF may promote DA neuron survival by regulating autophagy， and thus serves as a critical molecule in PD progression.