This study is designed to investigate the effect of low temperature plasma (LTP) on the apoptosis of CNE-2Z cell (human nasopharyngeal carcinoma cell line) and the potential mechanisms. We find out that LTP provoked the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in CNE-2Z cells and significantly inhibit the cell viability and induce cell apoptosis. Furthermore, the antioxidant N-acetyl cysteine (NAC) almost completely blocked LTP-induced apoptosis. LTP triggered mitochondrial and endoplasmic reticulum (ER) stress-induced apoptotic pathways indicated by significant upregulation of CHOP, p53, and Bax-to-Bcl-2 ratio. This work will provide the molecular theoretical basis of clinical application of LTP for the treatment of human nasopharyngeal carcinoma.[GRAPHICS].