Abstract: While tumor immunotherapy has improved the prognosis of many patients, immunotherapy drug resistance develops in most tumors. Studies of new targets and therapies are needed to overcome this challenge. Growing evidence indicates that Siglecs function in immune checkpoints. Siglecs belong to a family of salivary acid-binding immunoglobulin-like lectins. The majority of Siglecs are immunosuppressive transmembrane proteins that bind to sialic acid-containing glycans on glycoproteins and glycolipids. Sialoglycan-Siglec interactions contribute to tumor immune escape and are strongly correlated with poor prognosis in tumor patients. This review will discuss Siglec function in immune checkpoints, and how the interaction between sialic acid and Siglecs regulates the tumor microenvironment to exert therapeutic effects.