Arsenic (As) is a metal with potentially toxic effects on different organisms. Hydrogen sulfide (H2S) plays a vital role in alleviating heavy metal toxicity through reducing oxidative stress in plants and animals. However, the function of H2S in alleviating arsenic toxicity in yeast cells remains unclear. In this study, we investigated the effects of NaHS (exogenous physiological H2S) on cell death and its possible mechanism in yeast cells induced by sodium arsenite. Our results showed that sodium arsenite could induce yeast cell death, and pretreatment with 0.05 mmol/L NaHS significantly alleviated sodium arsenite-induced cell death. Under sodium arsenite conditions, the content of malondialdehyde (MDA) increased together with inhibition of the catalase (CAT) activity, and the expression of CTT1 and CTA1 were down-regulated. However, the activity of the superoxide dismutase (SOD) increased, and SOD1 gene expression was markedly up-regulated in the group that treated by sodium arsenite. When the yeast cells pretreated with NaHS, the intracellular ROS and MDA content decreased significantly, and the activity of SOD and CAT increased significantly compared to the arsenic treatment alone. Our findings indicated that NaHS alleviated sodium arsenite-induced yeast cell death is mediated mainly by enhancing the antioxidant defense system.