Cadmium (Cd) is a non-essential heavy metal responsible for soil and water pollution mainly by anthropogenic activities, threatening the ecosystem by impairing the health of organisms including animals and plants. In light of plants’ resistance to cadmium, researchers have tried to reveal the detoxification mechanisms for potential biotechnical and agricultural uses. Herein, the correlation between epigenetic regulations and the cadmium stresses in the Arabidopsis thaliana model was explored using a reverse genetics method. Around 200 epigenetic mutants were treated with different concentrations of cadmium while their traits in roots and shoots were identified for the selection of cadmium tolerant or cadmium sensitive mutations. Molecular biology techniques including RT-qPCR and ChIP-seq were applied to examine the upregulated or downregulated genes by the epigenetic mutation. As a result, a histone deacetylase mutation was discovered to exhibit tolerance to cadmium possibly due to upregulation in cadmium detoxification-related genes.