Mitochondrial dysfunction is implicated in pathogenesis of Parkinson’s disease (PD). Lycopene, a member of the carotenoid family of phytochemicals, exerts its neuroprotective effects by reducing oxidative damage and improving mitochondrial function in several experimental models. In an attempt to clarify the protective effect of lycopene on toxin-insulted dopaminergic neuronal death, the present study was carried out by using a typical PD-1-methyl-4-phenylpyridinium iodide (MPP+)-induced dopaminergic SH-SY5Y cellular model. SH-SY5Y cells were preincubated with different dose of lycopene for 2 h, followed by the challenge with 500 μM MPP+ for 24 h. It is found that lycopene attenuated MPP+-induced cytotoxicity, as evidenced by the improved cell viability and the decreased apoptotic rate. Additionally, lycopene suppressed the reactive oxygen species accumulation and lipid peroxidation caused by MPP+. Lycopene also ameliorated MPP+-induced mitochondria-derived ROS production and mitochondrial morphological changes. Furthermore, lycopene attenuated MPP+-induced opening of the mitochondrial permeability transition pore and the concomitant disruption of the mitochondrial membrane potential, reversed MPP+-induced reduction in ATP concentration and decreases in mitochondrial DNA copy numbers and mitochondrial RNA transcript levels. Together, the protective effects of lycopene against MPP+-induced cytotoxicity may be attributable to its roles in improving mitochondrial function. These data suggest that lycopene may provide a valuable therapeutic strategy for the treatment of PD.