Urokinase‑type plasminogen activator receptor (uPAR) serves as the receptor for uPA and the uPA‑uPAR complex initiates the extracellular matrix degradation cascade. In cancer, aberrantly elevated uPAR expression is associated with invasion and metastasis, as well as cancer proliferation and survival, thereby rendering uPAR an effective marker for prognosis and a target for therapy. Although uPAR is transiently expressed at limited amounts in normal tissues and certain non‑cancer pathological processes, their underlying mechanisms do not overlap with those of tumorigenesis. The present review summarized the fundamental function, signaling pathways and targeted therapeutic strategies, particularly immunotherapy targeting uPAR, as well as its differential roles in non‑cancer and cancer tissues, to objectively evaluate whether this classic molecular pathway is of enduring research value for future study.