Humans are most exposed to the heavy metal cadmium (Cd), known as neurotoxic. However, it is unclear how selenium (Se) protects neurons from damage caused by increased Cd-induced neurotoxicity in SH-SY5Y cells and how the TRPM2 channel functions in this process. In this study, we examined the impact of Se on CdCI2-induced oxidative neurotoxicity and cell death in SH-SY5Y cells by modifying the TRPM2 channel. The Se and TRPM2 channel antagonist 2-APB was added to prevent CdCI2-induced neurotoxicity in SH-SY5Y cells. Cell viability rate was determined between groups by CCK-8 assay. GSH, MDA, and ROS levels were determined in the cells with ELISA kits. Our results showed that the TRPM2 channel plays a vital role in forming CdCI2-induced damage to cells by using the TRPM2 antagonist in the study. We also observed that Se reduced CdCI2-induced neurotoxicity by reducing TRPM2 channel activation by suppressing oxidative stress of cells. We conclude that Se therapy and TRPM2 channel blocking can reduce CdCI2-induced neurotoxicity based on our investigation, which examined the protective impact of Se and the involvement of the TRPM2 channel in CdCI2-induced SH-SY5Y cells for the first time. Keywords: Cadmium, Selenium, SH-SY5Y cells, TRPM2 channel