TSLP (thymic stromal lymphopoietin), recognized as a biomarker similar to interleukin-7 (IL-7), is primarily produced by epithelial cells located in the surface barrier, particularly in the gastrointestinal tract, respiratory system, and skin tissue. The role of TSLP in malignancy varies depending on the context. Its impact on cancer progression can either promote or inhibit tumors, influenced by the diverse genetic foundations and classifications of different cancers. Human studies generally link TSLP expression with pro-tumor activity, except in colorectal cancer cases. Conversely, mouse model studies reveal an anti-tumor role for TSLP in pancreatic, breast, and skin tumors, particularly with high systemic TSLP levels. Overall, while TSLP role in cancer is strongly established, manipulation of its expression for therapeutic targets requires further understanding of its pro-tumor and anti-tumor roles in the various types of cancers. This chapter aims at investigating the TSLP functions and its associated mechanisms in various types of malignancies.