As a major component of the stromal microenvironment of various solid tumors, the extracellular matrix (ECM) has attracted increasing attention in cancer-related studies. ECM in the tumor stroma not only provides an external barrier and framework for tumor cell adhesion and movement, but also acts as an active regulator that modulates the tumor microenvironment, including stromal immunity. Fibronectin (Fn), as a core component of the ECM, plays a key role in the assembly and remodeling of the ECM. Hence, understanding the role of Fn in the modulation of tumor stromal immunity is of great importance for cancer immunotherapy. Hence, in-depth studies on the underlying mechanisms of Fn in tumors are urgently needed to clarify the current understanding and issues and to identify new and specific targets for effective diagnosis and treatment purposes. In this review, we summarize the structure and role of Fn, its potent derivatives in tumor stromal immunity, and their biological effects and mechanisms in tumor development. In addition, we discuss the novel applications of Fn in tumor treatment. Therefore, this review can provide pro-spective insight into Fn immunotherapeutic applications in tumor treatment.