Purinergic signaling is involved in many biological processes. Adenosine 5′ - triphosphate and other extracellular nucleotides act as endogenous ligands to bind and activate purinergic receptors for signaling and indicate their potential. A variety of widely expressed purinergic receptors have been found in human tumor tissues and tumor cell lines which are activated by extracellular ATP in inflammatory and hypoxic tumor environments and play a key role in affecting tumor cell metabolism proliferation and metastasis. Specifically P2X receptors belong to ligand - gated ion channels while P2Y receptors belong to G protein - coupled receptors. Activation of these receptors affects key biological processes such as intracellular Ca 2+ concentration cell cycle apoptosis and cell migration. In different types of tumors different purinergic receptor subtypes show different expressions and effects. For example P2X7 promotes tumor cell proliferation in neuroblastoma while P2Y12 inhibits tumor cell clonogenicity and migration in glioblastoma. In addition the activation of purinergic receptors also affects the immune response and therapeutic effect in the tumor microenvironment. Drugs targeting different purinergic receptor subtypes can affect the growth and metastasis of tumor cells and even enhance the effect of immunotherapy. This article reviewed the functional research progress of a variety of purinergic receptors and discussed their roles in different cancers and further understand its potential as a target for anti-tumor drugs.