Cadmium (Cd) is a heavy metal that is toxic to both plant growth and human health. Kinetin, a precursor of cytokinin, plays crucial roles in the response of plants to abiotic stress. However, the mechanism underlying kinetin detoxification in Cd-induced stress remains poorly understood. In this study, we observed a significant increase in endogenous kinetin levels in both rice shoots and roots under Cd stress. Furthermore, the application of exogenous kinetin resulted in a reduction in hemicellulose content within cell walls, thereby reducing the cell wall's capacity to bind Cd and limit its entry into cells. In addition, exogenous kinetin downregulated the transcript levels of genes associated with Cd uptake and root-to-shoot translocation while simultaneously upregulating the transcript levels of genes involved in Cd efflux from cells and sequestration into vacuoles, consequently leading to reduced Cd accumulation in rice plants. Moreover, kinetin significantly decreased nitric oxide (NO) accumulation in response to Cd stress, potentially facilitating detoxification during Cd-induced stress through a NO-dependent mechanism. Overall, our findings suggest that kinetin enhances rice's tolerance to Cd by increasing the cell wall's ability to bind Cd and regulating gene expression related to Cd accumulation. These mechanisms may be NO-dependent and could potentially inform the development of new strategies for mitigating Cd toxicity in agricultural systems. © 2023 Elsevier B.V.