Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN) with the presence of alpha-synuclein inclusions termed Lewy bodies. The aggregation of alpha-synuclein into oligomeric species affects neuronal viability, having a causal role in the development of PD. The neuroprotective effects of protocatechuic acid (PAc) have been reported. However, the effects of PAc on tyrosine hydroxylase (TH) and alpha-synuclein in rat pheochromocytoma (PC12) cells treated with 1-methyl-4-phenylpyridinium ion (MPP(+)) remains unclear. In this study, we demonstrated that PAc inhibited the cytotoxicity, apoptotic morphology, reduction of TH expression and abnormal oligomeration of alpha-synuclein in PC12 cells treated with MPP(+). Taken together, our results indicate that the neuroprotective effects of PAc on PC12 cells treated with MPP(+) is related to the inhibition of the oligomerization of alpha-synuclein.