Cadmium (Cd 2+ ) is a common toxic heavy metal ion. We investigated the roles of hydrogen sulfide (H 2 S) and cysteine (Cys) in plant responses to Cd 2+ stress. The expression of H 2 S synthetic genes LCD and DES1 were induced by Cd 2+ within 3 h, and endogenous H 2 S was then rapidly released. H 2 S promoted the expression of Cys synthesis-related genes SAT1 and OASA1, which led to endogenous Cys accumulation. The H 2 S and Cys cycle system was stimulated by Cd 2+ stress, and it maintained high levels in plant cells. H 2 S inhibited the ROS burst by inducing alternative respiration capacity (AP) and antioxidase activity. H 2 S weakened Cd 2+ toxicity by inducing the metallothionein (MTs) genes expression. Cys promoted GSH accumulation and inhibited the ROS burst, and GSH induced the expression of phytochelatin (PCs) genes, counteracting Cd 2+ toxicity. In summary, the H 2 S and Cys cycle system played a key role in plant responses to Cd 2+ stress. The Cd 2+ tolerance was weakened when the cycle system was blocked in lcddes1-1 and oasa1 mutants. This paper is the first to describe the role of the H 2 S and Cys cycle system in Cd 2+ stress and to explore the relevant and specificity mechanisms of H 2 S and Cys in mediating Cd 2+ stress.Cadmium (Cd 2+ ) is a common toxic heavy metal ion in the environment. It greatly affects the growth and development of plants and is harmful to human health through the food chain 1,2 . Because of its carcinogenic properties and its detrimental effects on the growth of organisms, Cd 2+ contamination of agricultural soil has become a critical concern. Preventing reduced growth and accumulation of Cd 2+ in harvested organs of plants growing on Cd 2+ -contaminated soils has become an urgent task as it can contribute to food safety. Thus, it is important to explore plant stress defense mechanisms and to find ways to reduce the Cd 2+ accumulation in grains.As a heavy metal not participating in redox reactions, Cd 2+ can easily dissolve in water and quickly be taken up by plant roots 3,4 . The physiological consequences of Cd 2+ toxicity in plants are chlorosis, stunted growth, and cell death, among others [5][6][7] . At the cellular level, Cd 2+ can alter protein structure and inhibit enzyme activity by binding to sulfhydryl and carbonyl groups and replacing essential co-factors of enzymes [7][8][9] . The overproduction of reactive oxygen species (ROS) is the primary response of plants to Cd 2+ with negative impact on cell function 10 . Further damage can be caused by ROS-independent, secondary mechanisms. Lipid peroxidation is the most deleterious effect caused by Cd 2+ -induced ROS 4 . Malondialdehyde (MDA), one of the decomposition products of lipid peroxidation, can modify active substrates in plant cells, including nucleic acids, proteins and saccharides 11 . To become resistant to Cd 2+ toxicity, plants have developed several strategies, such as inducing the