Cotton is a valuable industrial fiber-producing crop. However, soil salinization has brought serious yield and economic losses to cotton production. Appropriate application of potassium can improve the salt tolerance of crops and reduce salt damage, but the regulatory mechanism of potassium improves cotton adaptability to salt stress is still limited. In this study, transcriptome and metabolome analyses were performed on cotton roots treated with C (0 mM NaCl), S (150 mM NaCl) and SK (150 mM NaCl + 9.38 mM K2SO4), and verified by physiological indexes. The results showed that ion transport, hormone metabolism and reactive oxygen species (ROS) scavenging pathways played important roles in cotton root adaptation to salt stress. Salt stress caused oxidative damage and ion toxicity in cotton roots by disrupting hormone homeostasis and down-regulating the expression of potassium transporter and antioxidase-related genes. However, appropriate application of potassium alleviated the damage of salt stress on cotton by maintaining hormone and ion homeostasis and promoting the removal of ROS. In this study, the key biological pathways, regulatory genes and metabolites of potassium regulating cotton root adaptation to salt stress were determined, and the regulatory network diagram of genemetabolite interactions was constructed, which provides a new insight into the complex mechanism of potassium regulates salt adaptation in cotton and other crops, and will promote the progress of cotton genetic improvement and cultivation techniques.