Triphenyltin (TPT) widely exists as environmental pollutant, but its toxicity towards nerve cells and the related mechanism remain unclear. In this research, SHSY-5Y cells were exposed to TPT, and the cellular proteasome activity, I kappa b proteins, Bax and alpha-synuclein levels were investigated. The results show that TPT can inhibit the cellular proteasome activity, and result in the accumulation of ubiquitinized proteins. TPT exposure can change the protein levels of I kappa B, Bax, and alpha-synuclein, affect NF kappa B pathway, activate the process of cell death, and induce alpha-synuclein aggregation. Our results indicate that TPT exposure can lead to neuotoxicity.