The WRKY transcription factor plays a crucial role in plant stress adaptation. Our research has found that WRKY6 inSolanum tuberosum(potatoes) is closely related to cadmium (Cd) tolerance. Therefore, investigating the mechanism of StWRKY6 in plant resistance to Cd toxicity is of great scientific importance for food safety. This research further analyzed the gene structure and functional regions of the nuclear transcription factor WRKY6 in potatoes, discovering that StWRKY6 contains W box, GB/box, ABRE, and other elements that can act as a nuclear transcription regulatory factor to execute multiple functional regulations. The results of the heterologous expression of StWRKY6 in Arabidopsis under Cd stress showed that the overexpression line (StWRKY6-OE) had significantly higher SAPD values and content of reactive oxygen species scavenging enzymes than the wild type, indicating that StWRKY6 plays a crucial role in protecting the photosynthetic system and promoting carbohydrate synthesis. Transcriptome analysis also revealed that the Cd-induced expression of StWRKY6 up-regulated many potential gene targets, including APR2, DFRA, ABCG1, VSP2, ERF013, SAUR64/67, and BBX20, which are involved in Cd chelation (APR2, DFRA), plant defense (VSP2, PDF1.4), toxic substance efflux (ABCG1), light morphology development (BBX20), and auxin signal (SAUR64/67). These genes coordinate the regulation of Cd tolerance in the StWRKY6 overexpression line. In summary, this study identified a potential gene set of the co-expression module of StWRKY6, providing useful evidence for the remediation of Cd-contaminated soil and the genetic breeding of low Cd-accumulating crops, thereby ensuring food safety.