G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that play a crucial role in signal transduction and cellular communication. GPCR proteins are involved in a wide range of physiological processes, including cell growth, migration, and survival. Dysregulation of GPCR protein expression has been implicated in the pathogenesis of various diseases, including cancer, and GPCR proteins have been shown to modulate these processes in various types of cancer, highlighting their importance as potential therapeutic targets. In this review, we summarize the expression regulation of GPCRs in cancer cells, update the various ways by which the abnormal expression of GPCR protein affects the behavior of tumor cells, and discuss the current research directions and potentially facing problems of strategies on GPCR-targeting therapy.