Integrins are vital surface adhesion receptors that mediate interactions between the extracellular matrix (ECM) and cells and are essential for cell migration and the maintenance of tissue homeostasis. Aberrant integrin activation promotes initial tumor formation, growth, and metastasis. Recently, many lines of evidence have indicated that integrins are highly expressed in numerous cancer types and have documented many functions of integrins in tumorigenesis. Thus, integrins have emerged as attractive targets for the development of cancer therapeutics. In this review, we discuss the underlying molecular mechanisms by which integrins contribute to most of the hallmarks of cancer. We focus on recent progress on integrin regulators, binding proteins, and downstream effectors. We highlight the role of integrins in regulating tumor metastasis, immune evasion, metabolic reprogramming, and other hallmarks of cancer. In addition, integrin-targeted immunotherapy and other integrin inhibitors used in preclinical and clinical studies are summarized.