Tagetes patula L. (T. patula) is a Cd hyperaccumulator plant with high ornamental value and strong resistance. Understanding the molecular mechanisms of Cd tolerance in hyper-accumulating plants is important for improving phytoremediation efficiency. This investigation studied to how Cd affected T. patula's physiological characteristics and molecular alterations. With the increase of Cd concentration, chlorophyll content, and root biomass decreased; the activities of antioxidant enzymes such as GST, SOD and POD increased. Initially, Cd accumulated mainly in the root and then transferred upward to the leaves. The molecular mechanisms of T. patula after 150 mg/kg and 250 mg/kg treatments were analyzed by transcriptome. In total, 5429 and 6546 differentially expressed unigenes were identified. Phenylpropanoid biosynthesis and phenylalanine metabolism were identified as key pathways in reaction to Cd stress. In addition, many differential genes involved in the response to Cd stress were identified, including heavy metal transporter protein genes, genes and transcription factors related to Cd detoxification. These results indicate that the response of T. patula to Cd was multifaceted, laying the foundation for studies to improve its tolerance to toxic metals.